Seminar 20 Oct – Malaria Prevention: Progress and Prospects

BRCCH Seminar 20 Oct - Malaria Prevention: Progress and Prospects

 

Visual: Swiss TPH, fairpicture

 

Description:  The BRCCH cordially invites you to join our seminar addressing the progress and prospects of malaria prevention. Prof Simon Draper (University of Oxford, UK) will highlight the challenges, successes and future developments of vaccine-based solutions. Then, Prof Melissa Penny (Swiss TPH) will share her work on data analytics and modelling as product development support. Finally, Prof Evelyn Korkor Ansah (University of Health and Allied Sciences, Ghana) will provide insights into vaccine implementation and equitable distribution.

When: Thursday, October 20th, 2022 from 15:00-16:30 CET

Where: Hybrid Zoom / Kollengienhaus, Hörsaal 116, Petersgraben 50, 4051 Basel

Zoom Registration: HERE

In-person Registration (encouraged but not mandatory): HERE

Schedule:

      • Welcome by Prof Marcel Tanner (Swiss Academy of Arts and Sciences and Swiss TPH)
      • Prof Simon Draper (University of Oxford, UK): Malaria Vaccines – Recent Advances and Future Challenges (20 min)
      • Prof Melissa Penny (Swiss TPH): Data Analytics and Modelling Supporting Novel Malaria Prevention (20 min)
      • Prof Evelyn Korkor Ansah (University of Health and Allied Sciences, Ghana): Lessons from Malaria Vaccine Implementation in Ghana (20 min)
      • Q&A and Closing
      • Networking Apéro

Keynote speakers:

Prof Simon Draper

University of Oxford, UK

Simon Draper is a Professor of Vaccinology and Translational Medicine. The research undertaken in the Draper group focuses on the development of novel and improved approaches to blood-stage malaria vaccine design, as well as aiming to better understand molecular mechanisms of vaccine-induced immunity to blood-stage malaria infection. In particular, the group’s research interests span: strategies for improved vaccine antigen identification; development of improved vaccine delivery strategies; assessment of quantitative antibody correlates of protective immunity, and assessment of human vaccine-induced antibody responses to guide structure-based immunogen design and to better understand protective mechanisms of immunity.

A critical strength of the group is a strong dual focus on preclinical vaccine development in parallel with early-phase clinical vaccine testing and experimental medicine studies. There is a strong translational emphasis, with the most promising new approaches and/or candidate vaccines feeding into the Blood-Stage Malaria Clinical Trials Programme.

Prof Melissa Penny

Swiss Tropical and Public Health Institute & University of Basel, Switzerland

Melissa Penny is a professor and Head of the Disease Modelling research unit at Swiss TPH. She has more than 16 years of experience developing mathematical and computational models to provide quantitative evidence to support infectious disease control and elimination decisions, particularly for product development and policy decisions on new interventions.

She leads and has led international multi-institute consortia to provide evidence to WHO and other stakeholders for decision-making on new malaria interventions. This evidence includes the likely public health impact and cost-effectiveness of new interventions, such as the world’s first malaria vaccine RTS,S/AS01 (2015 and 2021), and, more recently, novel immune therapies. Her recent research focuses on developing data- and epidemiology-informed mathematical models and associated algorithms to understand pathogen, host, and intervention dynamics and to inform decisions during product development through implementation and policy recommendations. This work includes new approaches using mechanistic models to inform quantitative target product profiles for novel malaria tools. Her group has also developed new models of SARS-CoV-2 dynamics and applied them to inform decisions on novel interventions against COVID-19. She is also a member of several WHO scientific or technical working groups and WHO Guideline Development Groups.

She also leading a BRCCH-funded project to inform novel medical interventions against SARS-Cov-2 (find out more here).

 

Prof Evelyn Korkor Ansah

University of Health and Allied Sciences, Ghana

Evelyn Korkor Ansah is the Director of the Centre for Malaria Research. She is a Public Health Physician, an Epidemiologist, a fellow of the Ghana College of Physicians and Surgeons and a Rockefeller Foundation Bellagio Fellow. Prof Ansah was the Vice Chair of the Global Fund’s Technical Review Panel (TRP) to combat HIV/AIDS, Tuberculosis and Malaria until 2019. She currently serves on the WHO’s Malaria Policy Advisory Committee (MPAC) and Malaria Elimination Oversight Committee (MEOC). In addition to this, she serves on the Independent Evaluation Panel (IEP) of the Global Fund to fight HIV/AIDS and Malaria. Prior to this, she served on the Technical Evaluation Reference Group (TERG) of the Global Fund, the Bellagio Academic Selection Panel of the Rockefeller Foundation, and the Steering Committee of the ACT Consortium (involving over 15 institutions in several countries).

Her key research interests are malaria case management, diagnostics, health systems, maternal health and capacity building for health research. To this end, she has conducted a number of multi-country and local studies including clinical trials and health systems research.

Getting Ahead of Viral Evolution Using Artificial Intelligence

Getting Ahead of Viral Evolution Using Artificial Intelligence

It has been nearly three years since the emergence of SARS-CoV-2, and it is plainly apparent the world faces a future reality of an ever-changing virus that is here to stay. We now have diagnostics, vaccinations and therapies to fight COVID-19, but the continued emergence of new viral variants means that we too must continually assess, adapt and respond to these threats. Prof Sai Reddy (ETH Zurich and BRCCH) and his colleagues are doing just that by using artificial intelligence to prepare for future variants.

Within the scope of the BRCCH’s Fast Track Call for COVID-19 research funding programme, Prof Reddy and his consortium have developed an artificial intelligence method, deep mutational learning, that predicts the ability of SARS-CoV-2 variants to bind to human cells and escape antibodies. This prediction for current and prospective variants may guide the future development of therapeutic antibody treatments and next-generation COVID-19 vaccines. The information can also be generated in real-time to aid faster public health decision-making. And from a global health perspective, the development of vaccines that protect against future variants improves their efficaciousness and may even help to address vaccine inequity.

In this conversation, Prof Reddy joins BRCCH to discuss this exciting new method. He explains how this research came to be, “This work was enabled by the generous support of the Fondation Botnar to promote, in the very early stages of the pandemic, innovation to overcome the challenges that were known at the time of the peak of the pandemic. But at that time, new challenges, like variants, breakthrough infections and the evolution of SARS-Cov-2, were not necessarily anticipated.

The Fondation’s early commitment to supporting the FTC programme enabled us to respond quickly to this changing pandemic landscape and actually to come up with a new strategy focused on SARS-CoV-2 specifically, instead of applying a band-aid approach using existing, and perhaps inadequate or outdated, methods.”

In the journal Cell, Prof Reddy and his team published this new method called deep mutational learning, a machine learning-guided protein engineering technology that can help us understand how a new variant will affect vaccinated or previously infected people, potentially in real-time as the variant emerges in a population.

Graphical abstract: "Selection and emergence of SARS-CoV-2 variants are driven in part by mutations within the viral spike protein and in particular the ACE2 receptor-binding domain (RBD), a primary target site for neutralizing antibodies. The researchers develop deep mutational learning (DML), a machine learning-guided protein engineering technology, which is used to interrogate a massive sequence space of combinatorial mutations, representing billions of RBD variants, by accurately predicting their impact on ACE2 binding and antibody escape. A highly diverse landscape of possible SARS-CoV-2 variants is identified that could emerge from a multitude of evolutionary trajectories. DML may be used for predictive profiling on current and prospective variants, including highly mutated variants such as Omicron, thus guiding the development of therapeutic antibody treatments and vaccines for COVID-19." -Taft et al. 2022

 

The ability to make these predictions have big implications for how we may face the future of the pandemic. For example, researchers could use this method to identify therapeutic antibodies or develop next-generation vaccines that have the broadest coverage and the potential to be most effective against current and emergent variants. From a public health perspective, the method could be used to perform surveillance and a real-time assessment, so that governing bodies could leverage that wealth of information to guide public health decisions sooner and more effectively.

“This method allows us to prospectively gather lots and lots of information about the potential evolutionary trajectories of any virus and that makes us a little bit more proactive, rather than always waiting and being a step behind the virus. This may even allow, someday, for us to get ahead of viral evolution.” - Prof Reddy

Additionally, this technology has the potential for societal impact and improving vaccine inequity. In the current global health situation, countries differ greatly in access to vaccines. The inequity is exacerbated by time. The more time that passes between getting a vaccine and when it was designed, the higher the probability of it being less efficacious against variants that have since emerged. In other words, people who receive vaccinations later run the risk of not being protected against the newest variants and only being protected from older variants that are no longer circulating in the population.

“Part of the importance of this method could be that we eventually can make vaccines that have broader coverage and have a longer shelf life of being useful. So even if populations do not get immediate access, they are still at least getting an effective vaccine. This is where there's an opportunity for us to make a difference in global and public health. Our research team cannot solve the problems with manufacturing, distribution and the economics of vaccinations, but we can at least contribute to the science behind the design of vaccines, which represents a highly important part of the science value chain on the path to global translation.” -Prof Reddy

The science behind the technology is indeed innovative, as ETH News explains:

Since viruses mutate randomly, no one can know exactly how SARS-CoV-2 will evolve in the coming months and years and which variants will dominate in the future. In theory, there is virtually no limit to the ways in which a virus could mutate. And this is the case even when considering a small region of the virus: the SARS-CoV-2 spike protein, which is important for infection and detection by the immune system. In this region alone there are tens of billions of theoretical possible mutations.

That’s why the new method takes a comprehensive approach: for each variant in this multitude of potential viral variants, it predicts whether or not it is capable of infecting human cells and if it will be neutralized by antibodies produced by the immune system found in vaccinated and recovered persons. It is highly likely that hidden among all these potential variants is the one that will dominate the next stage of the COVID-19 pandemic.

To establish their method, Reddy and his team used laboratory experiments to generate a large collection of mutated variants of the SARS-CoV-2 spike protein. The scientists did not produce or work with live virus, rather they produced only a part of the spike protein, and therefore there was no danger of a laboratory leak.

The spike protein interacts with the ACE2 protein on human cells for infection, and antibodies from vaccination, infection or antibody therapy work by blocking this mechanism. Many of the mutations in SARS-CoV-2 variants occur in this region, which allows the virus to evade the immune system and continue to spread.

Although the collection of mutated variants the researchers have analysed comprises only a small fraction of the several billion theoretically possible variants – which would be impossible to test in a laboratory setting – it does contain a million such variants. These carry different mutations or combinations of mutations.

By performing high-throughput experiments and sequencing the DNA from these million variants, the researchers determined how successfully these variants interact with the ACE2 protein and with existing antibody therapies. This indicates how well the individual potential variants could infect human cells and how well they could escape from antibodies.

The researchers used the collected data to train machine learning models, which are able to identify complex patterns and when given only the DNA sequence of a new variant could accurately predict whether it can bind to ACE2 for infection and escape from neutralizing antibodies. The final machine learning models can now be used to make these predictions for tens of billions of theoretically possible variants with single and combinatorial mutations and going far beyond the million that were tested in the laboratory. (Read full article)

Background

This research was developed by a BRCCH-supported multi-disciplinary consortium working together and as part of a larger BRCCH research programme, the Fast Track Call for COVID-19 research (FTC). The programme aims to enable research that will help mitigate medical and public health challenges and contribute tangible solutions to reduce global disease burden due to COVID-19. Lead investigator Sai Reddy is Vice Director of BRCCH and a professor in the Department of Biosystems Science and Engineering, ETH Zurich

“This specific project was inspired and commenced as an extension of the original FTC project, which was initially based on developing a testing method for SARS-CoV-2 using a high throughput DNA sequencing method. As new variants emerged, such as Omicron this last winter, and the ensuing wave of breakthrough infections, we realised we could extend our work to develop technology and an approach where you could prospectively identify what combinations of mutations might escape from antibodies.” -Prof Reddy

 

Research article:

Taft JM, Weber CR, Gao B, Ehling RA, Han J, Frei L, Metcalfe SW, Overath M, Yermanos A, Kelton W, Reddy ST. 2022. "Deep Mutational Learning Predicts ACE2 Binding and Antibody Escape to Combinatorial Mutations in the SARS-CoV-2 Receptor Binding Domain." Cell. journal pre-proof. https://doi.org/10.1016/j.cell.2022.08.024

Related articles:

ETH News article "Preparing for Future Coronavirus Variants Using Artificial Intelligence"

MORE about Prof Reddy’s FTC research DeepSARS

MORE about the BRCCH-supported COVID-19 research

 

 

 

 

BRCCH 2022 Image Contest

BRCCH Image Contest

The BRCCH warmly invites all BRCCH Early Career Researchers involved in a BRCCH-supported project to participate in the second edition of the BRCCH Image Contest. Submit your images of your scientific work for a chance to win a sponsorship* to attend a scientific conference of your choice. 

Images should visually reflect the research done in your BRCCH project during 2022. They could, for example, show lab, clinical or field work, depict certain methods used, or visualise results or data, or show the goals of the project. Winning images will be selected based on aesthetics and alignment with the BRCCH scientific scope.

Please send us your image(s) by email to contact@brc.ch with a descriptive caption and a credit of the image(s) by Friday, 2 December 2022.

Details and conditions at bottom of page.

Last year's winners

The BRCCH received many stunning and inspiring entries in the 2021 contest. Here are the three winning entries.

2021 contest winner Ronja Rappold (ETHZ) who is working on a MIP project. The image shows a mouse cross-section of cecal tissue with food content. It is stained with Hematoxylin and Eosin to visualise the nuclei and the extracellular matrix, respectively. Researchers use these stainings to assess the pathological state of tissues. Visual: Ronja Rappold

2021 contest winner Keith Gunapala (University of Basel) who is working on a PEP project. In this image, human embryonic stem cells were engineered to have 23 chromosomes. These haploid embryonic stem cells can be used to more easily model human diseases and identify therapeutic approaches because having only one copy of a gene to work with makes the results of causation much easier to study. Blue shows DNA within a haploid cell, red indicates histones and green is the centromere of the chromosome. Visual: lab of Nissim Benvenisty

2021 contest winner Michele Gregorini (University of Basel) who is working on a FTC project. In this image, BRCCH researchers are developing an affordable and accurate “rapid PCR test” with the goal of making advanced diagnostics available in point-of-care and resource-limited settings. Visual: Diaxxo AG

    About the 2021 Winners:

    Ronja Rappold, MSc, is a PhD student working with Prof Viola Vogel and Prof Emma Wetter Slack in the Department of Health Sciences and Technology (D-HEST) at ETH Zurich. She is highly interested in studying how mechanobiological cues affect cell signalling, more particularly the mechanobiological impact on intestinal inflammation. In a Multi-Investigator Project, she is investigating pathology-associated extracellular matrix changes occurring in the gastrointestinal tract and other disease-implicated organs. Using immunohistochemistry and histology techniques, high-resolution imaging and advanced image analysis, she is aiming to find mechanobiological readouts that could be used as early diagnostic markers in rare genetic disorders of metabolism.

    With her BRCCH Image Contest prize, Ronja attended the 2022 EMBL Symposium: Mechanobiology in development and disease in Heidelberg, Germany.

     

    Dr Michele Gregorini is a postdoctoral researcher at the Institute for Chemical and Bioengineering (ICB) at ETH Zurich. Dr Gregorini is a pioneer fellow of ETH Zurich and his PhD thesis focuses on the agile development of a variety of chemical devices. In a Fast Track Call for COVID-19 Research project, his main focus has been the development of hardware and software for the peakPCR platform, a series of thermocycling devices performing PCR analysis in a fraction of the usual time. Dr Gregorini obtained his PhD in Prof Wendelin Stark’s group after finishing his master’s degree in mechanical engineering at ETH Zurich.

     
    With his BRCCH Image Contest prize, Michele attended the 18th Münchner AIDS- und COVID-Tage in Munich, Germany.

    Dr Keith Gunapala is a postdoctoral fellow in the lab of Prof Verdon Taylor at the Department of Biomedicine of the University of Basel. In a Postdoctoral Excellence Programme project, His research interests lie in understanding human brain development using organotypic culturing and cerebral organoids. He aims to use these platforms to better understand normal human brain development, neurodevelopmental disorders, and find novel therapeutic strategies. He holds a PhD from the University of Basel in neurobiology.

    With his BRCCH Image Contest prize, Keith attended the International Society for Stem Cell Research (ISSCR) 2022 Annual Meeting in San Francisco, USA.

    Attending the ISSCR was a game changer for me. I was able to listen to cutting-edge unpublished work that widened my horizons but directly impacted my project as well. There was one talk about the epigenetics of FMR1 in stem cells which was highly relevant and made me turn my project to a different direction to find potential drug targets. Without the support of the BRCCH I would not have been able to broaden my project without the opportunity to hear that fantastic talk.” - Dr Keith Gunapala

    BRCCH Supports Travel Fellowships for the 7th World One Health Congress

    BRCCH Supports Travel Fellowships for the 7th World One Health Congress

     

    The BRCCH provides three travel fellowships (up to 5’000 SGD each / approximately 3'400 CHF) to PhD students and early career scientists aiming to attend the 7th World One Health Congress (WOHC 2022) taking place in Singapore on November 7-11, 2022. Early career researchers involved in paediatric health or medicine and residing in low- and middle-income countries are encouraged to apply.

    Apply by 31 July: More on the WOHC 2022 website. Submit application on the registration webpage.

    About the congress:

    The theme for the 7th World One Health Congress is Integrating Science, Policy and Clinical Practice: A One Health Imperative Post-COVID-19. To capture the multifaceted One Health paradigm, the WOHC 2022 will bring together five distinct tracks over five days: One Health Science, Pandemic Preparedness and Health Systems Resilience, Policy, Environment and Biosecurity, Impact on and Innovations in Clinical Practice, and Antimicrobial Resistance. The programme will feature renowned keynote speakers, plenary lectures from experts, scientific sessions with abstract presentations and panel discussions on urgent and emerging topics.

     

     

     

    Conversation with Prof Sai Reddy

    DeepSARS: Sequencing and testing at the same time

    A new scientific platform called DeepSARS, developed by Prof Sai Reddy, BRCCH Vice Director and Professor of Systems and Synthetic Immunology at ETH Zurich, could support viral testing and tracking for future pandemics: While current diagnostic testing and genomic surveillance methods are being done separately, DeepSARS is able to perform both tasks simultaneously. This allows for earlier detection of emerging variants and profiling mutations at the population level. In this conversation, Prof Reddy joins journalist Irène Dietschi to discuss the consortium’s exciting new findings.

    Graphical abstract: DeepSARS uses molecular barcodes (BCs) and multiplexed targeted deep sequencing (NGS) to enable simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2. Image courtesy of Yermanos et al. 2022

     

    The ongoing COVID-19 pandemic remains a major global health concern with novel variants of SARS-CoV-2, such as alpha, beta, gamma, delta and omicron, that are continuously emerging and resulting in new waves of infection. Potentially exacerbating the situation, many of the masking and social distancing rules are relaxed around the world.

    The latest variant of SARS-CoV-2, omicron, with over 50 mutations is able to infect at a greater capacity than previous strains and often possesses substantial immune evasion, leading to many breakthrough infections in vaccinated or previously infected individuals. 

    Genomic surveillance of SARS-CoV-2 has been a vital component in the monitoring of the pandemic, providing valuable information for guiding public health decisions. However, despite the fact that the SARS-CoV-2 genomes from infected patients have been sequenced at unprecedented levels, they still represent a small fraction of the total number of global infections. And countries vary widely in how they prioritize viral genome sequencing. What makes it even more problematic is that in the countries with low sequencing rates, they also tend to have high infection rates and are therefore at an especially high risk for new mutations to evolve. They are hotspots for new variants.

    Key region: the receptor binding domain

    That is where DeepSARS comes into play. "A number of researchers have previously embraced the idea that sequencing could be used not just for genomic surveillance, but also for diagnostic testing", says immunology professor Sai Reddy, Vice Director of the BRCCH. Prof Reddy, who is the principal investigator of the Laboratory for Systems and Synthetic Immunology at ETH Zurich, has actually pursued this idea to a practical level. In a paper published recently in BMC Genomics, he, his team and collaborators have established a scientific concept which has proven that sequencing and testing can be done simultaneously. Their system is called DeepSARS.

    "One of the main challenges of the project was to determine which sites in the viral genome would yield maximum diagnostic and genomic information while maintaining sufficient coverage for each site", explains Prof Reddy. One region which is most associated with new variants is the spike protein of SARS-CoV-2, and within the spike protein it is particularly the so-called receptor binding domain – the site where the virus attaches itself to the host receptor ACE2 – where mutations most likely occur.

    This receptor binding domain also happens to be the target site of neutralizing antibodies, generated from either vaccination or previous infection. Mutations which emerge from this region can influence variants’ attachment to host cells, potentially making them more transmissible and are allowing them to escape from neutralizing antibodies. "Therefore, when we are developing sequencing tests, it is very important to get information about the receptor binding domain", says Prof Reddy. "It was a central part for the design of DeepSARS."

    Experimental protocol and ‘targeted deep sequencing’

    Once this was established, Sai Reddy and colleagues proceeded in a stepwise manner to develop the DeepSARS system. "First we elaborated an experimental protocol, which is in fact very similar to the protocol in which all PCR tests are performed", says Prof Reddy. "The main difference is that we added little personalized markers to each sample of the PCR, so that when you perform a genomic sequencing experiment you know which patient it came from." This procedure is called molecular barcoding.

    The second step the researchers undertook was to identify regions for what they call "targeted deep sequencing". Prof Reddy: "Targeted deep sequencing means reducing the viral genome from 30’000 RNA bases to about 20 percent of that number - 6000 bases. And it means identifying those 20 percent of sites which give us information that will likely track the evolution of the virus, as well as identify emerging variants." To achieve that, Reddy and colleagues performed an extensive computational analysis (i.e., computational phylogenetics). In this way they identified target candidates of the viral genome and then implemented them in the experimental protocol.

    Proof of concept on patients’ sample

    Next, they validated their data on synthetic RNA templates of SARS-CoV-2, based on genomic sequences recovered early in the pandemic. "That allowed us to do very precise experiments to detect the amount of viral material, which was as low as 10 copies of the virus per sample", Prof Reddy explains.

    The final step was testing DeepSARS on samples from patients. "We had samples from 30 patients, and we were able to show, based on nasal swabs or saliva, that the DeepSARS testing assay was very close to performing at the same level of diagnostic detection as a traditional PCR test", says Prof Reddy. And: "It was able to provide enough information about genomic surveillance to classify viral evolution, and whether there were any variants or not." In short: DeepSARS works. With the proof of concept, its science and technology may be regarded as well established.

    A solid foundation for future pandemics

    The exciting question is, could DeepSARS be applied at a larger scale? Could it even be deployed in the current COVID-19 pandemic? "DeepSARS certainly has a lot of potential", says Prof Reddy. "But right now, while we’re still in the COVID-19 pandemic, it wouldn’t make much sense to replace the current infrastructure for diagnostics and genomic surveillance with a new system." As Prof Reddy explains, that would implicate numerous changes in the logistics and regulations of the on-going pandemic, which, among other aspects, would be far too costly and require extensive regulatory approval.

    Yet Sai Reddy is collaborating with public health experts in Switzerland as well as with clinicians at University Hospital Basel and other partners, discussing future applications, including clinical testing of DeepSARS. The goal is to examine the system at a larger scale. "We have shown that DeepSARS can be rapidly adapted for identification of emerging variants and for profiling mutational changes at a small scale but for a pandemic, this requires population level implementation", says Prof Reddy. "Practically speaking, DeepSARS could be of immense benefit in for future pandemics or possibly as SARS-CoV-2 transitions to an endemic stage."

    Background

    DeepSARS was developed by a BRCCH-supported consortium where bioengineers, immunologists, computational biologists and clinical scientists work together and as part of a larger BRCCH research programme, the Fast Track Call for COVID-19 research (FTC). The programme aims to enable research that will help mitigate medical and public health challenges and contribute tangible solutions to reduce global disease burden due to COVID-19.

    This specific project aims for rapid transfer of these state-of-the art diagnostic methods across Switzerland and many other countries around the world, leading the way for innovative population level surveillance approaches of future variants and other disease outbreaks.

     

    Interview: Irène Dietschi

    Research article:

    https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-022-08403-0

    Yermanos A, Hong KL, Agrafiotis A, Han J, Nadeau S, Valenzuela C, Azizoglu A, Ehling R, Gao B, Spahr M, Neumeier D, Chang CH, Dounas A, Petrillo E, Nissen I, Burcklen E, Feldkamp M, Beisel C, Oxenius A, Savic M, Stadler T, Rudolf F & Reddy ST. 2022. "DeepSARS: simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2." BMC Genomics. DOI:v10.1186/s12864-022-08403-0

    MORE about the BRCCH-supported COVID-19 research by Prof Sai Reddy and consortium.

     

     

     

    BRCCH Seminar 6 July: Refining Paediatric Treatments for All

    BRCCH Seminar 6 July: Refining Paediatric Treatments for All

    **Update July 19th, 2022** Thank you to everyone that attended our hybrid seminar! We had a great turnout-- in case you missed the presentations or you would like to watch them again, you can now stream them below or on our YouTube channel.

    Visual: Kiran Kuruvithadam

     

    Description:  The BRCCH cordially invites you to join our seminar looking at Refining Paediatric Treatments for All. This event will highlight the research progress of Prof Thomas Erb (UKBB) on how to reduce the risk associated with the use of mechanical ventilation in children, and the efforts to improve competence in paediatric anaesthesia in Switzerland. Then, Dr Marianne Schmid Daners (ETH Zurich) will provide an overview of the challenges of paediatric hydrocephalus treatment. Finally, Prof Kokila Lakhoo (University of Oxford) will present her work in low- and middle-income countries on providing surgical treatments to children in need.

    When: Wednesday, July 6th, 2022 from 16:00-17:30 CET

    Where: Hybrid Zoom / UKBB seminar room, Spitalstrasse 33, 4056 Basel

    Zoom Registration: HERE

    In-person Registration (encouraged but not mandatory): HERE

    Schedule:

        • Welcome by BRCCH Director Prof Georg Holländer
        • Prof Thomas Erb & his team (UKBB): "Safety first in children undergoing anaesthesia and sedation!" (25 min)
        • Dr Marianne Schmid Daners (ETH Zurich): "Challenges of paediatric hydrocephalus" (20 min)
        • Prof Kokila Lakhoo (University of Oxford): "Addressing the global health challenges for children with surgical needs in low- and middle-income countries" (40min, online)
        • Closing

    Seminar Archive

    Prof Thomas Erb (UKBB) presents "Safety first in children undergoing anaesthesia and sedation!" originally given on July 6th, 2022.

    Dr Marianne Schmid Daners (ETH Zurich) presents"Challenges of Paediatric Hydrocephalus"originally given on July 6th, 2022.

    Prof Kokila Lakhoo (University of Oxford) presents "Addressing the Global Health Challenges for Children with Surgical Needs in Low- and Middle-income Countries" originally given on July 6th, 2022.

    Keynote Speakers:

    Prof Kokila Lakhoo

    Nuffield Department of Surgical Sciences, University of Oxford

    Prof Kokila Lakhoo is a consultant paediatric surgeon at the Children’s Hospital in Oxford and the University of Oxford. She is also Chair of the International Forum for the British Association of Paediatric Surgeons and the President of the Global Initiative for Children’s Surgery (GICS). She is developing paediatric surgery through a link in Tanzania and has collaborative research projects in Malawi and South Africa. Besides general paediatric surgery and ambulatory surgery, her special interests are global health, fetal counselling, neonatal surgery, paediatric tumour surgery, paediatric thoracic surgery and specialist gastrointestinal surgery.

     

    Prof Thomas Erb

    University Children's Hospital Basel

    Prof Thomas Erb completed his medical training with board examinations in anaesthesiology and critical care. Subsequently, he moved to Durham, North Carolina, USA, where he worked in the Pediatric Cardiology Program at Duke University. There, he also obtained a master of health sciences in clinical research. Returning to Switzerland in 2000, Prof Erb started his clinical research programme in the Department of Anaesthesiology at the University of Basel and University Children’s Hospital Basel (UKBB). In 2010, he became Titular Professor of Anaesthesiology, and in 2011 he was made Head of the Division of Paediatric Anaesthesia at UKBB. His clinical interests and research are focused on the effects of anaesthetic conditions on airway and lung mechanics in children. He is currently leading the BRCCH-funded COVent project aiming to develop practical solutions that reduce the risks associated with the use of mechanical ventilation, especially those associated with low-cost/do-it-yourself ventilators and off-label use that are now available in many resource-limited settings.

     

     

    Dr Marianne Schmid Daners

    Institute of Design, Materials and Fabrication, ETH Zurich

    Dr Marianne Schmid Daners graduated from ETH Zurich as a mechanical engineer. She then completed her doctorate on the topic of “Adaptive Shunts for Cerebrospinal Fluid Control” at ETH Zurich’s Institute for Dynamic Systems and Control. Dr Schmid Daners heads the institute’s Biomedical Systems Group as a senior scientist. At the interdisciplinary interface of clinical research and engineering, her passion is the pathophysiological understanding of the dynamics of the intracranial and cardiovascular systems. Her research focuses on the modelling, control and testing of biological systems, as well as on the development and control of biomedical devices for the treatment of heart failure and hydrocephalus.

    Takeaways from Panel Discussion: Impact of COVID-19 on Global Paediatric Health

    Takeaways from Panel Discussion: Impact of COVID-19 on Global Paediatric Health

    On May 24th 2022, a panel of experts highlighted several important facets of the consequences that COVID-19 pandemic has on the global paediatric health situation:

    - decreased access to vital child healthcare services like newborn care and immunisation
    - increased poverty
    - more nutritional and physical activity deprivation
    - mental impairment
    - compromised learning and loss of a caregiver

    Moderator: Prof Julia Dratva, Zurich University of Applied Sciences (ZHAW) & University of Basel, Switzerland

    Panel members: Prof Yvonne Maldonado, Stanford University, USA; Prof Alan Stein, University of Oxford, UK; Dr Marc Birkhölzer, University of Basel, Switzerland; Prof Thomas Berger, Secretary and Chief Medical Advisor at NEO FOR NAMIBIA

    More about the event here.

    Find out more about our speakers and read about their takeaways below

     

    From left to right: Prof Julia Dratva, Dr Marc Birkhölzer, Prof Yvonne Maldonado, Prof Thomas Berger. (Prof Alan Stein joined remotely, not pictured)

     

     

    Prof Yvonne Maldonado

    Dr Marc Birkhölzer

    Prof Alan Stein

    Prof Thomas Berger

    Prof Julia Dratva

    Six Projects Selected for Principal Investigator Initiative

    Principal Investigator Initiative (PII)

    The Botnar Research Centre for Child Health (BRCCH) is pleased to announce six research projects within its new initiative, the Principal Investigator Initiative (PII). The PII aims to drive interdisciplinary research that addresses critical challenges in global paediatric health and medicine. BRCCH’s PII projects bring together researchers from its four partner institutions and international partners who will deliver step-changing innovations and intervention strategies across paediatric health diagnosis, disease treatment and prevention with global reach. Each project is supported with up to 1 million CHF for a duration of four years. Research activities will start in Summer 2022.

     

     

    The BRCCH supports the following projects:

    Visual Analysis of Long Lasting Insecticidal Nets to Maximise Universal Access

    Long-lasting insecticidal nets (LLINs) are the mainstay of malaria control. However, more than 50% of people living in endemic areas are currently unprotected because LLINs often develop holes and wear out sooner than their expected lifespan. The consortium led by Dr Sarah Moore, Dr Amanda Ross (Swiss TPH) and Prof Philippe Claude Cattin (UniBas) will develop a digital tool enabling national malaria control programs to improve planning for programmatic LLIN distribution, monitoring of LLIN quality and selection of the best product for use according to contextual settings. Increasing mosquito net lifespan will optimise resource use, increase the protection of children and reduce malaria transmission in LMICs.

    Team members: Dr Sarah Moore (Swiss Tropical and Public Health Institute), Prof Philippe Claude Cattin (University of Basel), Dr Robin Sandkühler (University of Basel), Dr Amanda Ross (Swiss Tropical and Public Health Institute); Sumaiyya Thawer (Swiss Tropical and Public Health Institute), Prof Fabrizio Tediosi (Swiss Tropical and Public Health Institute), Emmanuel Mbuba (Ifakara Health Institute, Tanzania), Dr Zawadi Mboma (Ifakara Health Institute, Tanzania), Frank Chacky (Ministry of Health, Tanzania).

     

    Alex: Design, Development and Evaluation of a Digital Health Assistant for Paediatric Asthma

    Poor adherence to medication and insufficient monitoring are key factors that contribute to inadequate asthma control in children and adolescents. The consortium led by adjunct Prof Edgar Delgado-Eckert (UKBB and UniBas) and Prof Elgar Fleisch (ETH Zurich) aims to improve asthma control in adolescents using a smartphone-based digital health assistant designed for regular and sustained remote disease monitoring and patient coaching. They will also harness digital and AI-based approaches to assess a patient’s health state passively, i.e., minimising the patient’s burden in the process of disease monitoring. Finally, the consortium will assess the feasibility and scalability of the digital health assistant in the socio-economic setting characteristic of low-to-middle income countries.

    Team members: Adjunct Prof Edgar Delgado-Eckert (University Children’s Hospital Basel and Department of Biomedical Engineering at University of Basel), Prof Elgar Fleisch (Center for Digital Health Interventions at ETH Zürich), Prof Urs Frey (University Children’s Hospital Basel), Dr Filipe Barata (Center for Digital Health Interventions at ETH Zürich), Prof Nicole Probst-Hensch (Swiss Tropical and Public Health Institute), Prof Sorin Man (Emergency Clinical Hospital for Children, Romania).

     

    OptiThyDose: Intelligent Digital Decision Support Tool to Personalise Dosing for Children with Thyroid Diseases

    Hypo-/hyperthyroidism manifests at birth or during childhood. Prompt and adequate medical treatment is key to protecting cognitive and physiological development in affected children. Dose optimisation is complex as there is a wide spectrum of thyroid disease severity and activity, developmental pharmacology, and inter-individual variability in drug kinetics and response in these children. As such, there is frequent over- and under-dosing despite international treatment guidelines. The consortium led by Prof Gabor Szinnai and Prof Marc Pfister (UKBB) aims to develop an intelligent decision support tool - OptiThyDose - that optimises and computes personalised dosing for a given child afflicted with hypo- or hyperthyroidism. They will conduct international multi-centre studies to validate the clinical use of OptiThyDose in different socio-economic settings. This innovative research work is supporting families and caregivers with the ultimate goal to enhance cognitive and somatic outcomes in affected children, independent of socio-economic status.

    Team members: Prof Gabor Szinnai (PI, University Children’s Hospital Basel), Prof Marc Pfister (Co-PI, University Children’s Hospital Basel); Prof Michel Polak (Hôpital Necker-Enfants Malades, France), Prof Marco Cappa (Ospedale Pediatrico Bambino Gesù, Italy), Prof Lusine Navasardyan (Arabkir Medical Centre, Armenia), Prof Johannes Schropp (University of Konstanz, Germany).

     

    Investigating Early Signs and Developmental Course of Personality Disorders in Young People

    Personality disorders (PDs) are frequent mental illnesses that have devastating effects on both afflicted individuals and society. Until recently, PDs were primarily diagnosed in adulthood, although it is now well-established that their onset begins in childhood and adolescence. With the introduction of the Levels of Personality Functioning (LPF) in Section 3 of the DSM 5 in 2013 a new concept to diagnose PD was proposed. A very similar approach was adapted for the ICD 11, previous age restrictions for diagnosing PDs have been lifted. The consortium led by Dr Marc Birkhölzer (UniBas) aims to investigate if this new concept is valid and useful to diagnose and assess personality impairments in children and adolescents, in the same way as it does in adults. Through multi-site longitudinal studies, they will also develop approaches to investigate early signs and the progression of PDs in an equivalent way across different cultures, age groups and socio-economic settings.

    Team members: Dr Marc Birkhölzer (University of Basel), Dr Kirstin Goth (University of Basel), Prof Hojka Gregoric Kumperscak (University Medical Center Maribor, Slovenia), Prof Natalia Zvereva (Moscow State University, Russia), Prof Sylvia Kaaya (The Muhimbili University of Health and Allied Sciences, Tanzania), Dr Delia Birle (University of Oradea, Romania), Prof Rasa Barkauskiene (Vilnius University, Lithuania), Dr Moises Kassin (Universidad Iberoamericana Ciudad de México, Mexico), Prof Eva Möhler (Saarland University Hospital, Germany), Prof Carla Sharp (University of Houston, USA), Prof Diane Purper-Ouakil (University of Montpellier, France), Prof Kathrin Sevecke (Innsbruck University Clinic for Psychiatry, Austria), Dr Lea Sarrar (MSB Medical School Berlin, Germany), Dr Sefa Cosgun (Private Clinic Istanbul, Turkey), Dr Felix Euler (Juvenile Forensic Department, Zurich), Dr André Della Casa (Psychiatric University Clinic, Zurich).

     

    Feasibility and Economic Evaluation of Improved Child Deworming

    Parasitic worm infections are still very common, particularly among children living in areas with limited access to safe drinking water and adequate sanitation. Moreover, children are at the highest risk of morbidity associated with chronic worm infections. The consortium led by Prof Jennifer Keiser, Prof Fabrizio Tediosi and Prof Peter Steinmann (Swiss TPH) will evaluate the introduction of a new combination therapy for soil-transmitted helminth infections into routine neglected tropical disease control activities in Uganda. The consortium will assess the feasibility, acceptability and cost-effectiveness of this deworming treatment, develop delivery toolkits for effective child deworming tailored for local settings and support policy change at national and international levels. This project will contribute directly to the advancement of worm infection management affecting poor and marginalised children in LMICs.

    Team members: Jennifer Keiser (Swiss Tropical and Public Health Institute), Fabrizio Tediosi (Swiss Tropical and Public Health Institute), Peter Steinmann (Swiss Tropical and Public Health Institute); Adriko Moses (Ministry of Health, Uganda).

     

    New Tools for Early Diagnosis and Decentralised Treatment of Buruli Ulcer

    Buruli ulcer (BU) is a chronic necrotising skin disease, caused by Mycobacterium ulcerans. BU primarily affects children in West and Central Africa and most infections occur in remote, rural areas where patients have limited access to appropriate interventions. The consortium led by Prof Daniel H. Paris (Swiss TPH) and Prof Janos Vörös (ETH Zurich) aims to develop a simple point-of-care diagnostic test and a simplified, rapid treatment for BU that can be implemented at the primary healthcare and community levels. This project will enable rapid diagnosis and early treatment of BU, preventing long-term suffering, stigmatisation and permanent disabilities in afflicted children.

    Team members: Prof Daniel H. Paris (Swiss Tropical and Public Health Institute), Prof Janos Vörös (ETH Zürich), Prof Gerd Pluschke (Swiss Tropical and Public Health Institute), Dr Alexander Tanno (Hemetron AG).

    About the Call: The initial call for applications was launched in Summer 2021. 23 applications were submitted on November 5th 2021, with 53 (Co-) Investigators involved and a total requested budget of 20.2 million CHF. All applications were evaluated by an independent, international review panel. The panel recommended six projects for funding (success rate of ∼26%). The BRCCH Board approved these recommendations in Spring 2022.

    Archive Application Documents

    Impact of COVID-19 on Global Paediatric Health – Panel Discussion

    Impact of COVID-19 on Global Paediatric Health

    Join us during an interactive debate with a panel of experts on the topic: How the COVID-19 Pandemic has affected Global Paediatric Health. The discussion will mainly focus on: i) mental health in young people, ii) disruption to life-saving paediatric health services such as immunisation and antenatal care.

    Tuesday, May 24th 2022 (16.00-17.15 pm CET)

    Moderator: Prof Julia Dratva, Zurich University of Applied Sciences (ZHAW) & University of Basel, Switzerland

    Panel members: Prof Yvonne Maldonado, Stanford University, USA; Prof Alan Steiner, University of Oxford, UK; Dr Marc Birkhölzer, University of Basel, Switzerland; Prof Thomas Berger, Secretary and Chief Medical Advisor at NEO FOR NAMIBIA

    Find out more about our speakers below

    The event is taking place in a hybrid format:

    The number of seats at Basel Biozentrum is limited, please register here.

    Interested in joining virtually? Sign up here!

    For more information, contact Dr Amandine Bovay, BRCCH Scientific Officer and Development Manager (amandine.bovay@brc.ch)

    *Update 1 June 2022: In case you missed the event, you can read the discussion takeaways here.

    Programme Speakers:

    Prof Yvonne Maldonado
    Division of Infectious Diseases, Department of Pediatrics
    Department of Epidemiology and Population Health                                 Stanford University School of Medicine, USA

    Yvonne Maldonado is Professor of paediatrics, epidemiology, and population health, and Chief of the division of paediatric infectious diseases at the School of Medicine, Stanford University. She also currently serves as Stanford Medicine’s Senior Associate Dean of Faculty Development and Diversity. Prof Maldonado's research focuses on the epidemiology and prevention of viral infectious diseases such as paediatric HIV, polio, measles and Ebola. Her work on mother-to-child transmission of HIV in sub-Saharan Africa is credited for preventing hundreds of thousands of newborns from acquiring HIV. She also leads research on the development and implementation of vaccines in low- and middle-income countries.

    Visual: Stanford University

    Prof Julia Dratva
    Institute of Public Health, ZHAW Zurich University of Applied Sciences, Switzerland
    Medical Faculty, University of Basel, Switzerland

    Prof Julia Dratva is a public health expert with a focus on child and adolescent health and early life factors of health and disease. She is the Head of the Public Health Research Unit at the Zurich University of Applied Sciences (ZHAW) and an Assistant Professor in the Medical Faculty at the University of Basel.

    Prof Dratva is a medical doctor by training with a background in internal medicine. She also holds a Master degree in Public Health and a Specialist Certification (FMH) for "Prevention and Public Health". She has a particular interest in the life course approach to health and disease in research and teaching, addressing vulnerable groups and vulnerable time spans. She also has research interests in cardiovascular health, health monitoring, health literacy and digital health.

    Prof Alan Stein
    Department of Psychiatry, University of Oxford, UK

    Alan Stein is Professor of Child & Adolescent Psychiatry at the University of Oxford, Honorary Professor in the School of Public health at the University of Witwatersrand and a member of the faculty of the African Health Research Institute, South Africa. His main area of research concerns the development of children and adolescents in the face of adversity. Ultimately the priority is to develop interventions. He has led three Lancet series on: i) The mental health of internally displaced and refugee children, ii) Perinatal mental health, iii) The communication of life-threatening conditions to children.

    Prof Thomas Berger
    Secretary and Chief Medical Advisor at NEO FOR NAMIBIA - Helping Babies Survive

    Prof Thomas Berger is a paediatrician specialised in neonatology and intensive care. With more than 25 years of experience in neonatology in various high-income countries, he decided to share his knowledge with physicians and nurses in less privileged countries. Therefore, he and his wife founded the non-profit organisation NEO FOR NAMIBIA – Helping Babies Survive in 2017. The team has just launched their 14th mission in Rundu State Hospital to improve neonatal and paediatric care in Namibia.

    Dr Marc Birkhölzer
    Psychiatrist, University of Basel, Swizterland

    Dr Marc Birkhölzer is currently a senior physician at the Juvenile Forensic Department of the Psychiatric University Clinics of Basel (UPK). His research focuses on personality disorders. Over the years, he has built an extraordinary network of collaborators in countries all over the world.

    A New Frontier in Diagnosing Gut Health

    A New Frontier in Diagnosing Gut Health

    Every year, more than 200 million children worldwide do not reach their developmental potential. This is primarily due to infectious diseases as well as malnutrition and related disorders. Normal gut development and function are critical for determining a child’s development and health throughout life. Despite this, diagnostics that can measure the health status of the gut are severely lacking.  As part of the BRCCH’s Multi-Investigator funding programme, Prof Randall Platt (ETH Zürich), Prof Andrew Macpherson (University Hospital Bern) and fellow consortium members seek to develop a non-invasive, microbe-based diagnostic that is capable of sensing and recording the status of the gut.

    In a new groundbreaking study published in Science*, Prof Platt, Prof Macpherson and co-authors have achieved the first critical steps towards making this ambitious idea a reality.

    Behind this work is the innovative Record-seq technology pioneered by Prof Platt in 20181. The technology is based on CRISPR-engineered bacteria that can sense and create a molecular record of changes in their surrounding environment over time. These bacteria, or ''transcriptional recorders'' can then be analysed via sequencing approaches to reveal the history of events that they encountered. This technology holds enormous potential to provide real-time information on the status of the gut environment, which could then be harnessed to guide personalised therapeutic interventions.

    In this new study, the researchers first set out to understand how the transcriptional recorders behave in a real-life gut environment and what they are able to report on whilst travelling through the intestine. The team demonstrated that these bacteria survive and traverse through the gut of mice, and that they can be successfully collected from faecal samples for further analysis. Importantly, the study revealed that the transcriptional recorders are able to capture important biological information throughout all regions of the gut. This represents a major advance over current omics-based technologies that are used to study the gut, as they are unable to provide insights into intestinal regions that are more difficult to access, such as the proximal colon.

    The CRISPR-engineered bacteria (or transcriptional recorders) create molecular records of information about their surrounding environment as they transit through the gut. These bacteria can then be retrieved via faecal samples and their molecular records analysed through sequencing and computational methods. Image courtesy of Prof Randall Platt

     

    Following these exciting results, the team then embarked on testing if the transcriptional recorders can reliably report on two elements which are critical for determining gut health: nutrition and inflammation.

    To do this, mice were fed with different diets and the transcriptional recorders were collected from faecal samples over time. A Record-seq analysis revealed that these bacteria record unique molecular signatures that are diet-specific and are retained by the bacteria, even following a dietary switch. Therefore, not only are these transcriptional recorders capable of reporting on the real-time dietary status in vivo, these findings also suggest that they can provide a window into the nutritional history of the gut.

    The researchers then took one step further by studying the transcriptional recorders in a mouse model of gut inflammation, to mimic the local environment in the presence of gastrointestinal disease.  Remarkably, the team discovered that the molecular signatures recorded by the bacteria could be used to distinguish healthy mice from those with gastrointestinal inflammation. Moreover, they could also provide a read-out for measuring the severity and biological indicators of inflammation within the gut.

    Following this landmark work, we asked Prof Randall Platt about where the consortium plans to take Record-Seq from here:

    ''This highly collaborative and interdisciplinary project lays the groundwork towards realising the technology’s true potential for improving human health. The consortium is now focusing on translation, which primarily includes further rigorous testing in animal models of human conditions as well as ensuring robust safety and environmental containment of the genetically engineered bacteria''.

     

    *Read the paper: https://www.science.org/doi/10.1126/science.abm6038

    Schmidt F, Zimmermann J, Tanna T, Farouni R, Conway T, Macpherson AJ, Platt RJ: Noninvasive assessment of gut function using transcriptional recording sentinel cells. Science, 12 May 2022, doi: 10.1126/science.abm6038

    About the researchers 

    Professor Randall Platt is an Associate Professor at the Department of Biosystems Science and Engineering (D-BSSE) at ETH Zürich and the Department of Chemistry at the University of Basel.

    Professor Andrew Macpherson is Professor and Director of Gastroenterology at University Hospital Bern.

    Professors Platt and Macpherson, together with fellow consortium members, lead the BRCCH Multi-Investigator Project: Living Microbial Diagnostics to Enable Individualised Child Health Interventions.

    1 Related articles

    Recording device for cell history (ETH News 03.10.2018)

    Bacteria with recording function capture gut health status (ETH News 12.05.2022)

     

     

    BRCCH Early-Career Programme

    BRCCH's Early-Career Events 2021-2022

    The BRCCH endeavours to foster the development of aspiring young researchers who will pioneer the next frontiers in global paediatric medicine and health. The BRCCH’s Early Career Programme aims to provide unique opportunities for its community members to gain know-how in research areas at the heart of the Centre’s mission and to grow their global network.

    This upcoming year (late 2021-mid 2022), the BRCCH invites its early-career community members to join local and international speakers in a series of interactive workshops on topics across the Centre’s mandate.

    For more information and registration, contact Dr. Amandine Bovay, BRCCH Scientific Officer and Development Manager (amandine.bovay@brc.ch)

    Webinar: Community-based COVID-19 Testing in Lesotho and Zambia

    Webinar: Community-based COVID-19 Testing in Lesotho and Zambia

    Visual: SolidarMed & Swiss TPH

     

    Description:  The BRCCH cordially invites you to join us online for a webinar looking at Community-based COVID-19 testing in Lesotho and Zambia. This event will highlight research progress of the collaborative project between Dr Kwame Shanaube (Zambart) and Dr Klaus Reither (Swiss TPH) on the effects of community-led interventions in mitigating the COVID-19 epidemics in Lesotho and Zambia. The BRCCH and the European & Developing Countries Clinical Trials Partnership (EDCTP) partnered on a joint initiative to support multi-national collaborations for research to mitigate COVID-19, particularly in low- and middle-income countries.

    When: Wednesday, April 27th, 2022 from 15:30-17:00 CET

    Where: Online, Zoom seminar

    Registration: HERE

    Schedule:

        • Welcome by BRCCH Director Prof Georg Holländer
        • Keynote lecture by Dr Kwame Shanaube (Zambart), Dr Klaus Reither (Swiss TPH) & their research teams:
                1. Overview of the joint BRCCH-EDCTP project: Improving Access to SARS-CoV-2 Screening and Testing through Community-based COVID-19 Case-Finding and the Use of Digital Solutions in Lesotho and Zambia
                2. Comparing different approaches of community-based SARS-CoV-2 testing in Lesotho and Zambia
                3. Barriers and facilitators to SARS-CoV-2 testing at community-based testing sites
                4. Evaluation of SARS-CoV-2 tests and testing approaches
        • Plenary discussion
        • Closing

    Keynote Speakers:

     

     

    Dr Kwame Shanaube

    Zambart & School of Public Health, University of Zambia

    Dr Kwame Shanaube is Deputy Director of Research (Quantitative) at Zambart, a multidisciplinary research organisation that conducts a range of studies including clinical trials, epidemiological studies and laboratory-based diagnostic studies. She is a clinician with a Master’s degree in public health and a PhD in TB clinical epidemiology. She is also an honorary lecturer at the University of Zambia School of Public Health. Her research interests cover a wide range of disciplines, including TB/HIV epidemiology, community-based cluster randomised trials, operational research through evaluation of field diagnostics and adolescent health. She is also the country’s Principal Investigator for a large international TB consortium (the TREATS Project) and the overall Principal Investigator for the TREATS-COVID study, both funded by the EDCTP.

     

    Dr Klaus Reither

    Clinical Research Unit, Swiss Tropical and Public Health Institute

    Dr Klaus Reither is Head of the Clinical Research Unit and the leader of the Clinical TB Research Group at the Swiss Tropical and Public Health Institute (Swiss TPH). He oversees and coordinates clinical research projects conducted by Swiss TPH and his research responsibilities comprise the set-up, implementation, coordination and supervision of clinical research projects, with an emphasis on TB clinical trials at Swiss TPH’s international partner organisations such as the Ifakara Health Institute in Tanzania, the National Centre of Tuberculosis and Lung Diseases in Georgia and SolidarMed in Lesotho.

    Dr Reither is Lead Investigator of the BRCCH COVID-19 project: MistraL - Mitigation Strategies for Communities with COVID-19 Transmission in Lesotho Using Artificial Intelligence on Chest X-rays and Novel Rapid Diagnostic Tests. Together with Dr Kwame Shanaube, he also co-leads a BRCCH-EDCTP collaborative project on Improving Access to SARS-CoV-2 Screening and Testing through Community-based COVID-19 Case-Finding and the Use of Digital Solutions in Lesotho and Zambia.

     

    Conversation with Prof Alexandar Tzankov

    A Cell Fitness Marker for Predicting COVID-19 Outcomes

    COVID-19 is unpredictable. Identifying which COVID-19 patients are likely to develop severe disease versus those at lower risk of complications remains a major clinical challenge. In a recent collaborative study*, BRCCH-funded investigator Professor Alexandar Tzankov (University Hospital Basel) and co-authors discovered a novel biomarker that could be used to predict the prognosis of COVID-19 patients more accurately. In this conversation, Prof Tzankov joins journalist Irène Dietschi to discuss          the consortium’s exciting new findings.

     

    Assessing a patient’s risk of developing severe disease is difficult. Usually, individuals who test positive for SARS-CoV-2 are referred to their physician and sent home to isolate. Which patients will develop severe symptoms and require hospitalisation is largely unknown at this point. In a study published in EMBO Molecular Medicine, Prof Alexandar Tzankov and co-authors have now uncovered a means to predict the prognosis of COVID-19 patients more precisely: by using a genetic marker called hFwe-Lose, or simply Flower lose.

    Behind this discovery is a relatively recent finding: cells constantly compare their fitness with each other in the body. Collaborators of Prof Tzankov, Prof Eduardo Moreno (Champalimaud Centre for the Unknown, Portugal) and Prof Rajan Gogna (University of Copenhagen), previously identified that the human flower gene (hFwe) can be expressed in different forms, which mark cells as either winners or losers. Fit or 'winning' cells express a form of the flower gene called hFwe-Win, whereas unfit or 'losing' cells express hFwe-Lose. This allows the body to identify unhealthy cells that need to be eliminated.

    ''The balance of expression of these flower genes is very important physiologically'' says Alexandar Tzankov. ''Their correct expression is critical in embryo and organ development, as well as in diseases such as cancer. hFwe-Lose is a kind of lifetime document for the whole body.'' It can provide insights into how fit a person’s body is at a given moment: What a person’s biological age is, how much cumulative toxicity they have been exposed to during life, if they have pathological obesity, how well does their body handle high blood sugar and hypertension.

    In May 2020, Prof Tzankov had just published an autopsy study of 21 deceased COVID-19 patients, the first major observational cohort of its kind. Professors Morena and Gogna suspected that flower genes might play a role in the progression of COVID-19 and decided to reach out to Prof Tzankov. ''They suggested examining the tissues of deceased patients for hFwe-Lose, and that's what we did'' says Alexandar Tzankov. The team also examined hFwe-Lose in patients with co-morbidities such as hypertension, diabetes, obesity and chronic obstructive pulmonary disease (COPD). The results confirmed the researchers' original idea: ''In healthy lungs, the expression of hFwe-Lose is very low. In the lungs of patients with co-morbidities, its expression increases. In patients who died of COVID-19, it is very high'', Alexandar Tzankov explains.

    hFwe-Lose is a genetic marker than can be used to predict outcomes in COVID-19 patients. Source: EMBO Molecular Medicine (2021) 13:e13714; https://doi.org/10.15252/emmm.202013714

     

    The researchers then decided to go one step further: They analysed hFwe-Lose levels in nasopharyngeal swab samples collected from 283 COVID-19 -at that time unvaccinated - patients in Wisconsin, USA during the early waves of infection. The team discovered that the higher the hFwe-Lose level was in the nasal sample, the more likely the patient went on to develop severe disease and to undergo hospitalisation and/or die of COVID-19. Remarkably, using computational modelling, the team uncovered that hFwe-Lose levels could be used to predict the risk of hospitalisation and death with a high degree of accuracy. ''For about 85% of people for whom the level of hFwe-Lose predicted hospitalisation, they actually had to go to the hospital. For virtually no one who died, mathematical modelling predicted that they would not have died'' explains Alexandar Tzankov.

    hFwe-Lose is relatively straightforward to analyse via the same nasal swab used to test for SARS-CoV-2 infection. ''This makes hFwe-Lose a very useful biomarker for COVID-19 patients'' says Alexandar Tzankov. So what could this mean for clinicians? ''You could potentially identify at-risk COVID-19 patients early, instruct these patients to pay very close attention to symptoms and keep the threshold for hospitalisation lower. That way, emergency situations could possibly be avoided.''

    ''I admit that this is an optimistic scenario for the use of this marker - but it has the potential.''

     

    Interview: Irène Dietschi

    Research article: https://www.embopress.org/doi/10.15252/emmm.202013714

    MORE about the BRCCH-supported COVID-19 research by Prof Alexandar Tzankov and consortium.

    MORE about COVID-19 research by the pathology team at University Hospital Basel.

     

    Architecture Vision for BRCCH New Home

    Architecture Vision for BRCCH New Home

    visual: Guerra Clauss Garin Architekten

     

    In a press release by the City of Basel, the firm Guerra Clauss Garen Architekten is announced the winner of the anonymous project competition from a selection of 48 entries. The canton, over the course of the next few years, will restructure the building on the corner of Schanzenstrasse and Spitalstrasse in Basel. Located strategically next to the life sciences campus Schällemätteli, the building will be the home to 4-5 research groups of the BRCCH.

    Read the press release (in German) on Kanton Basel-Stadt's website.

    Webinar: Future of COVID-19 Research

    Webinar: Future of COVID-19 Research

    **Update October 28th, 2021 ** Thank you to everyone that attended our webinar! We had a great turnout-- in case you missed the presentations or you would like to watch them again, you can now stream them below or on our YouTube channel.

    visual: background image courtesy of National Institute of Allergy and Infectious Diseases

     

    Description: The BRCCH cordially invites you to join us online for a webinar looking at The Future of COVID-19 Research. This event will highlight significant research progress and the roadmap ahead related to immunology, epidemiology and bioengineering. Gain insights from our keynote speakers and engage with them during the Q&A panel discussion.

    When: Thursday, October 21st, 2021 from 15:00-17:00 CET

    Where: online, livestream Zoom seminar

    Schedule:
    Welcome by BRCCH Vice Director Prof Sai Reddy
    Keynote lecture by Prof Teresa Lambe OBE (University of Oxford)
         "Development and testing of the Oxford/AstraZeneca vaccine"
    Keynote lecture by Prof Benjamin Murrell (Karolinska Institutet)
         "Neutralizing SARS-CoV-2 variants"
    Keynote lecture by Prof Sai Reddy (ETH Zurich and BRCCH)
         "Identifying prospective variants of SARS-CoV-2 by deep mutational learning"
    Q&A Panel Discussion
    Closing

    Webinar Archive

    Prof Teresa Lambe OBE (University of Oxford) presents "Development and Testing of the ChAdOx1 nCoV-19/AZD1222 Vaccine" originally webcast on October 21st, 2021.

     

    Prof Benjamin Murrell (Karolinska Institutet) presents "Neutralizing SARS-CoV-2 Variants" originally webcast on October 21st, 2021.

     

    Prof Sai Reddy (ETH Zurich and BRCCH) presents "Identifying Prospective Variants of SARS-CoV-2 by Deep Mutational Learning" originally webcast on October 21st, 2021.

    Keynote Speakers:

    Prof Teresa Lambe OBE
    The Lambe Group for Emerging Pathogens
    The Oxford Vaccine Group and the Jenner Institute Laboratories
    Dept of Paediatrics, University of Oxford

    Assoc Prof Lambe will share her research insights into the immune response to SARS-CoV-2 and its vaccine. Her research group is part of the Covid-19 vaccine trial in the UK and has co-designed the vaccine and led the development and testing of the immune response after vaccination.

    Prof Lambe’s research investigates the establishment of protective immune responses following vaccination and the formation of adaptive immune memory. She is particularly interested in delineating the immune response post vaccination and also post natural infection to help develop vaccines and define correlates of protection. At the University of Oxford, her group uses platform technologies to develop vaccines against emerging and re-emerging pathogens. The group is currently developing vaccines against a number of outbreak pathogens including Crimean-Congo haemorrhagic fever virus, Lassa virus, Nipah virus, Influenza, Ebolavirus and coronaviruses.

    Visual: John Cairns/University of Oxford

    Prof Benjamin Murrell
    Department of Microbiology, Tumor and Cell Biology
    Karolinska Institutet

    Prof Murrell will speak about his work on the H2020 CoroNAb project, studying antibodies and isolating nanobodies against SARS-CoV-2.

    Prof Murrell's previous research interests surrounded the evolution of the HIV envelope protein, and antibodies against it. Recently, he has applied this expertise to SARS-CoV-2 and its variants. Together with colleagues, he has identified nanobodies from immunized alpacas that may be potential SARS-CoV-2 therapeutics, and has conducted preclinical immunization studies attempting to boost responses to SARS-CoV-2 variants. This work is part of the CoroNAb consortium research project, funded under Horizon2020 as part of the EU’s emergency funding call for COVID-19.

    Visual: Karolinska Institutet

    Prof Sai Reddy
    Laboratory for Systems and Synthetic Immunology
    Department of Biosystems Science and Engineering, ETH Zurich
    And Vice Director BRCCH

    Prof Reddy shares his recent work on developing a simultaneous diagnostic and genomic surveillance method for SARS-CoV-2 based on targeted deep sequencing. He will also present new data from his group related to identifying variants of SARS-CoV-2 using a novel method called deep mutational learning. 

    Prof Reddy’s research is focused on the emerging field of systems and synthetic immunology, with an aim towards developing technologies relevant to immunotherapy and biotechnology. He has developed a number of methods in systems immunology to improve our understanding of adaptive immunity, with a particular focus on immune repertoire sequencing. Recently, he founded two spin-off companies, deepCDR Biologics and Engimmune Therapeutics, which are both based on technologies developed in his research group on engineering antibodies or T cells.

    5 Early Career Researchers Selected for Postdoctoral Excellence Programme

    Postdoctoral Excellence Programme (PEP)

    The BRCCH announces five research projects within its new initiative, Postdoctoral Excellence Programme (PEP). The programme aims to foster the next generation of scientific leaders who will pursue interdisciplinary and step-changing research to address critical unmet needs and challenges in global paediatric health. Together with established Host Principal Investigators and Collaborators, PEP Fellows will implement highly translational and ambitious research proposals over the next three years.

    Patch-IT: Multi-Sensor Sensor Nodes for Continuous Vital Sign Monitoring to Identify Novel Digital Biomarkers for Sepsis Detection in Neonatal Intensive Care
    Neonatal sepsis has a high incidence globally and is a major cause of mortality worldwide. The project Patch-IT proposes a solution for improved neonatal sepsis monitoring and management. The team aims to develop a multi-sensor electronic epidermal system that incorporates wire-free, battery-free, non-invasive and autonomous monitoring of multiple vital signs continuously and in real time. The device will also employ in-sensor data analytics powered by state-of-the-art sensor-fusion algorithms to enable personalised patient monitoring. PEP Fellow Kanika Dheman (currently Department of Mechanical and Process Engineering, ETHZ) will join the lab of Dr Michele Magno (Department of Information Technology and Electrical Engineering, ETHZ).

    Developing Novel Drug Strategies for the Treatment of Fragile X by Functional Screening of Human Pluripotent Stem Cell Models
    Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability. FXS occurs due to epigenetic silencing, or non-expression, of a specific gene, FMR1. The goal of this project is to identify and test new drugs using human stem cells with the ability to induce re-expression of FMR1 and reverse FXS symptoms and effects. This proposal has 3 aims: 1. Establish baseline levels of FMR1 expression and downstream targets in normal and FXS stem cells 2. Screen novel categories of drug compounds and 3. Establish organoids, a type of tissue culture, from FXS stem cells to perform anatomical validation of drug efficacy. A PEP Fellow will conduct this work in the lab of Prof Verdon Taylor (Department of Biomedicine, University of Basel). The consortium also involves international collaboration with Prof Nissim Benvenisty (Department of Genetics, The Hebrew University of Jerusalem, Israel).

    Bioinspired, Low-Cost Device for Minimally Invasive Blood Sampling
    More than 70% of medical decisions depend on laboratory results and blood sampling is the most prevalent route for disease diagnosis and monitoring. The researchers propose to develop a versatile microsampling device for the collection of blood with minimal invasiveness, low manufacturing costs and sufficient volume retrieval for point-of-care tests or laboratory analysis. This device may be particularly suited for children where traditional blood draws using needles can cause distress. A prototype will be manufactured by 3D printing and validated pre-clinically ex vivo, in vivo and in combination with a commercially available point-of-care test for the detection of malaria. PEP Fellow Dr Nicole Zoratto (currently Department of Chemistry and Pharmaceutical Technologies, Sapienza University of Rome, Italy) will join the lab of Prof Jean-Christophe Leroux (Department of Chemistry and Applied Biosciences, ETHZ).

    Electronic Clinical Decision Support and Machine Learning to Improve Care Quality and Clinical Outcomes of Sick Young Infants in Low-Resource Settings
    Almost half of all deaths in children in the first five years of life occur in the neonatal and early infant period. Electronic Clinical Decision Support Algorithms (eCDSAs) can help guide health workers in appropriate and evidence-based patient evaluation and management, and have demonstrated benefit in improving clinical care for children. However, no such tool has been validated or tested for managing sick young infants in outpatient care settings in low- and middle-income countries (LMICs). The researchers will evaluate the effects of an eCDSA for neonates and young infants on the quality of care delivered and clinical outcomes among young infants in five LMICs. The investigators aim to enhance the prognostic and diagnostic performance of the algorithm using machine learning methods. PEP Fellow Dr Gillian Levine (currently Department of Epidemiology and Public Health, Household Economics and Health Systems Research Unit, Swiss TPH) will join the research group of Dr Tracy Glass (Department of Medicine, Swiss TPH).

    Harnessing Machine Learning and Mechanistic Modelling for Personalised Radiotherapy of Paediatric Diffuse Midline Glioma
    Diffuse midline glioma, a primary tumor within the most sensitive part of the brain, is a fatal disease primarily affecting children between 4-7 years of age. The project proposes to develop a digital health tool to guide doctors in designing optimal treatment strategies for affected children and their families. The overarching aim of this project is to build a treatment decision support platform facilitating personalised radiotherapy (RT) optimisation based on MRI for afflicted paediatric patients. The researchers will develop an analytical pipeline bridging mechanistic modelling and data-driven machine learning to refine patient stratification, discover imaging biomarkers, and inform RT scheduling and dosing by an individualised radiosensitivity score. PEP Fellow Dr Sarah Brüningk will continue to work in the lab of Prof Karsten Borgwardt (both of Department of Biosystems Science and Engineering, ETHZ), in collaboration with Prof Javad Nazarian (DMG Research Center, University Children’s Hospital Zurich).

    image: Joachim Pelikan, SwissTPH

      About the Call: The initial call for applications was launched in Fall 2020. 15 proposals were submitted with a combined total requested budget of 5’010’747 CHF. Following an external evaluation by a committee of international experts, 5 projects were recommended for full funding. The BRCCH Board approved these recommendations in May 2021.

      BRCCH Supports Travel Fellowships for Computational Biology Conference

      BRCCH Supports Travel Fellowships for [BC]2 Basel Computational Biology Conference

       

      The BRCCH provides three travel fellowships (1’666 CHF each) to PhD students and early career scientists aiming to attend the [BC]2 Basel Computational Biology Conference. Early career researchers involved in paediatric research and those from low- and middle-income countries are encouraged to apply.

      More information and APPLY at the [BC]2 website.

      The [BC]2 Basel Computational Biology Conference, September 13-15, 2021, will be more interdisciplinary than ever this year, with sessions on cancer and precision medicine, machine learning, clinical population genomics, pathogens and immune system, single-cell biology, evolutionary biology and ecology.  

      The conference will offer many opportunities for interactivity including the ELIXIR Innovation and SME Forum to learn about solutions for preventive medicine and the whole learning ecosystem of health, as well as tutorials and workshops providing an informal setting to discover and discuss about the latest bioinformatics methods.  

       

       

      BRCCH Physical Home by 2025

      BRCCH Physical Home by 2025

      visual: Kanton Basel-Stadt

       

      In a press release by the City of Basel, the canton shares news of its plans to build a new research building next to the life sciences campus Schällemätteli. The building, which will be completed by 2025, will host 4-5 research groups of the BRCCH. There is now an open anonymous project competition for a general planning team.

      Read the full press release (in German) on Kanton Basel-Stadt's website.

      Conversation with the Directors

      "We want to be measured by impact in global child health."

      It’s only a little more than two years since the BRCCH started operations. Since then, the research centre has already achieved important milestones, launched major research initiatives and sharpened its focus. In this conversation about the first two years and the future of the BRCCH, the centre's two directors, Georg Holländer and Sai Reddy, talk with journalist Felix Müller.

       

      Georg Holländer and Sai Reddy, it’s only a little more than two years since the BRCCH started operations. What would you call your biggest achievement during this initial phase?

      Georg Holländer: I'm delighted that we succeeded in putting together and starting a couple of aspirational and important programmes. First and foremost, I’d like to mention the Multi Investigator Programmes – we call them MIPs. Under their umbrella, we managed to draw together highly competitive research groups from different institutes to work on questions that otherwise could not be addressed in this fashion. The second achievement is that within these first two years, we have been able to successfully engage with our two partner universities in creating paths toward professorial posts as well as defining new areas that would align with the Centre’s research focus and benefit from further academic strength.

      Indeed, you came out of the starting blocks very fast …

      Sai Reddy: … which was not self-evident at all! ETH Zurich, University of Basel and our two additional partners, UKBB and Swiss TPH, have different philosophies, perspectives and historical strengths. This could have been a challenge for us, but we were able to pull together a very broad coalition of researchers from both universities in this short time. In a lot of ways, it's an extremely constructive and balanced constellation; we truly feel both interdisciplinary and inter-institutional. Both universities have embraced us and we, likewise, feel embedded in them.

      GH: And, thanks to the openness of these two universities and all four partners, we can count on an ongoing dialogue to underpin what we're trying to achieve.

      If you are embedded within the universities though, what about your own identity as the BRCCH?

      SR: Yes, since our current projects come from existing research groups at both universities, we are really part of them. With the recruitment of new professorships, it will help to establish a more unique identity over time.

      GH: My wish is that we will always be understood as a partner of equal standing. And that this applies to all our partners.

      When the founding of the BRCCH was announced in autumn 2018, another partner played a prominent role – Fondation Botnar, the Centre’s main donor. Was there ever any confusion about who was who?

      GH: In the beginning, we sometimes received communications that were clearly addressed to and meant to be for the foundation rather than the BRCCH. But over time it became easier for people to differentiate between the two entities. Especially the local community has embraced our BRCCH identity and our role as an independent research centre.

      COVID-19 has disrupted many organisations. How did the pandemic affect your activities?

      SR: When Fondation Botnar contributed a significant sum to a BRCCH fast track call for COVID-19 research projects, in just two weeks we received almost 80 applications.

      Two weeks? That’s an incredibly short time span to come up with a scientific research proposal.

      SR: The speed was driven by the motivation of the science community to respond swiftly. Science can move quickly if people collaborate and pull together. It is really amazing to look at what has already been learned and the data gathered about the virus to date. While not directly related to child health research, it is nevertheless critical for global health – and that means it’s critical for children’s health as the pandemic impacts families and society. Because the BRCCH also has a keen interest in supporting global health in low- and middle-income countries, areas where COVID-19 is going to continue due to lack of vaccine supply, we aim to stay on top of this and remain involved.

      GH: We have also started to see that the disease changes its face and that the causative virus mutates under selective pressure. With emerging new variants new questions also arise. And we see more and more young people, amongst them children, being affected. This area of research will clearly keep us engaged and challenged for an extended period of time.

      Indeed child health is a broad field. How do you keep the BRCCH focused?

      GH: There is so much that could and should be done in child health. But the impact and the sustainability of the BRCCH will come from the fact that we can look at and focus on a number of very relevant issues in global child health. These we can analyse in depth. The first two years of the BRCCH have focused on areas where we think, collectively with our partners, substantial step-changing contributions can be made. Even with the very generous funding available to us, we will only effectively contribute to change if we don't spread our activity too broadly and thus too thinly. We know it is important to stick to an overall strategic plan in order to deliver on our remit, but that doesn't mean the programme pursued is static – as we've just seen with COVID-19 research. We need to regularly check whether our priorities are still the correct ones; we are currently undergoing our first evaluation process as part of such an effort. After two years, this is a good time for external experts to review our research strategy and structure.

      How exactly will the external evaluation support your activities?

      GH: I hope it will provide us with a critical reflection of the focal scientific areas we have chosen and where we believe we can make a difference. The evaluation is expected to enable us to go forward in the correct direction and in a focused manner to deliver on what is needed.

      SR: This is difficult to say since it is an independent evaluation. But feedback about how to ensure our work is sustainable would be welcome, about how to build a sustainable centre that can grow as well – not simply keep to our path, but how we can be creative and adapt to that path as it unfolds.

      “Focus”, too, is a word you emphasise. So what is the BRCCH’s focus for the rest of 2021?

      SR: Soon a decision will be made on applications for a postdoc excellence programme in support of young researchers who are trying to find, and make a transition to, independent careers in child and adolescent health research. We also plan to roll out a principal investigator initiative, which is funding related to slightly smaller projects than our MIPs. Furthermore, we hope to start recruiting for three, out of a total of six, planned professorships by the end of the year.

      In which fields are the professorships?

      GH: One is in molecular diagnostics, and affiliated primarily with ETH and the Department of Biosystems Science and Engineering. The second professorship is related to digital medicine and health at University of Basel, Faculty of Medicine. And then we have a third one that is going to look at the ethics of childhood digital health and data. It too will be hosted by ETH and associated with the Department of Health Sciences and Technology.

      If we look to the future, to the end of your first 10 years in 2028: What headline would you like to read about your work?

      SR: I would hope to see a headline that would relate to our early MIPs – these are the ones that have the longest possible time to achieve their goals and make a clinical or translational impact.

      GH: I fully agree. We want to be measured by impact. But more than that – in 10 years when we look back, I hope we can say it was a good idea to bring these two universities together in the context of the BRCCH, and that through this collaboration we could make real contributions to global child health and well-being.

      To make an impact requires collaboration on local and global level. What about your networks and their growth in the past two years?

      GH: Given the design of the Centre, we largely depended on the competencies and contributions of researchers based at our partner institutions. This meant drawing on a broad network via our partner institutions at the beginning. But as we move into new and paediatric-related domains, we need to broaden and establish additional networks to complement existent expertise locally. So it’s gratifying that after only two years, we have a research portfolio that involves international collaborators from 18 countries – this augurs well for future outreach.

      Sai, Georg – final words: What were your most uplifting moments during the past two years?

      SR: For me it’s been the positive support received from all stakeholders around us – especially all our partners, our Board, Scientific Advisory Board, and clearly Fondation Botnar. Each step of the way has been met with positivity and enthusiasm. The trust we’ve been given has been really great.

      GH: Since Sai looked outside and commented on the interface with our partners, let me look inside. I'm particularly delighted to have a very collegial, hard-working team that shares a set of core values and goals that we wish to collectively achieve. I am happy to say that we are all pulling on the same strings, and singing from the same hymn sheet. That makes our endeavour so much more fun because it demonstrates a very deep common understanding about what we want to achieve.

      Thanks for your time. All the best.

       

      Interview: Felix Müller

      BRCCH and EDCTP Start a New Joint Initiative

      The BRCCH and EDCTP
      Start a New Joint Initiative

      The BRCCH and the European & Developing Countries Clinical Trials Partnership (EDCTP) are to support three multi-institutional, multi-country collaborations for research to mitigate the impact of COVID-19. Three collaborative projects are responding to the COVID-19 pandemic with research to improve the surveillance and management of COVID-19. The projects are a result of a synergistic Collaboration Initiative by EDCTP and the BRCCH to drive interdisciplinary efforts to combat global health challenges amidst the COVID-19 pandemic.

      The Collaboration Initiative:

      In 2020, each organisation launched its own emergency mechanism to support research in COVID-19. The EDCTP mechanism focused on efforts in sub-Saharan Africa to manage and/or prevent the spread of COVID-19 and targeted four thematic research gaps: therapeutics, diagnostics, serological testing, and understanding of the natural history of infection. The BRCCH Fast Track Call initiative focused on research within diagnostics, immunology and medical interventions that will help mitigate medical and public health challenges in the short term, and to also contribute solutions that will lead to better preparedness and reduced global disease burden in the long term.

      Realising the potential for collaborative efforts, the EDCTP and the BRCCH initiated dialogues between Principal Investigators (PIs) in their respective programmes. BRCCH-EDCTP consortia that wished to pursue a potential future collaboration were then invited to submit formal applications for external peer-review. The applications underwent evaluation in November 2020.

      This joint BRCCH-EDCTP Collaboration Initiative will support three projects that range from immunology to diagnostics and health screening strategies for COVID-19 in low- and middle-income country (LMIC) settings. The projects, which are a complementary extension to the ongoing research activities being funded by BRCCH and EDCTP, will launch in early 2021 and will be supported with 900,000 CHF in total funding over a period of two years. Involved BRCCH researchers are based in the centre's partner institutions: ETH Zurich, Swiss Tropical and Public Health Institute and the University Hospital Basel.

      Researchers do community outreach in remote areas in Lesotho in order to increase access to essential health services. Image: SolidarMed & Swiss TPH

       

      The Research:

      Improving Access to SARS-CoV-2 Screening and Testing through Community-based COVID-19 Case-Finding and the Use of Digital Solutions in Lesotho and Zambia
      In a collaboration between teams in Lesotho and Zambia, Dr Klaus Reither (Swiss TPH, BRCCH grantee for the MistraL project) and Dr Kwame Shanaube (Zambart, EDCTP grantee for the TREATS-COVID project) will investigate the effects of community-led interventions, rapid point-of-care diagnostics and swab self-collection in mitigating the COVID-19 epidemic in these African nations. The project will be carried out by 14-member consortium, including collaborators based at  the London School of Hygiene and Tropical Medicine, SolidarMed, FIND and KNCV Tuberculosis Foundation.

      African-European Partnership for Development and Deployment of Rapid SARS-CoV-2 RNA and Antigen Detection Assays
      Prof Janos Vörös, Prof Wendelin Stark (both ETH Zurich, BRCCH grantee for a Rapid Diagnostic Test project and for the peakPCR project, respectively) and Dr Ahmed Abd El Wahed (University of Leipzig, EDCTP grantee for the Suitcaselab project) aim to advance novel and rapid COVID-19 diagnostic technologies tailored for poor-resource and emergency settings. Including partners in France and seven African countries, the 13-PI consortium will co-develop a rapid lateral flow diagnostic assay, a portable PCR device operated in a mobile suitcase lab for use in low- and middle-income countries (LMICs). The consortium includes collaborators from the Institut Pasteur de Paris, Institut Pasteur de Dakar, Institute Pasteur de Madagascar, KNUST, University of Ibadan, INRB, University of Khartoum and Makerere University.

      COVID-19 Antibody Repertoires in Infection and Vaccination
      The project co-led by Prof Andreas Moor (ETH Zurich, BRCCH grantee for a B-Cell Immunity project) and Dr Julie Fox (King’s College London, EDCTP grantee for the COVAB project) aims to investigate B cell-mediated immunity to SARS-CoV-2 infection in different health states. Specifically, the consortium will investigate and compare the effects of SARS-CoV-2 infection on the antibody repertoire in patients who contract the virus through natural means, in COVID-19 patients who also suffer from HIV and in vaccinated individuals. This consortium involves four researchers from institutions in the UK and Switzerland (in addition to the two named above, the University Hospital Basel).

        About EDCTP:

        The mission of the European & Developing Countries Clinical Trials Partnership (EDCTP) is to reduce the social and economic burden of poverty-related diseases in developing countries, in particular sub-Saharan Africa, by accelerating the clinical development of effective, safe, accessible, suitable, and affordable medical interventions for HIV/AIDS, tuberculosis, malaria, neglected infectious diseases, lower respiratory tract infections, diarrhoeal diseases and infectious diseases of epidemic potential, including Ebola and COVID-19 . EDCTP is supported by the European Union under Horizon 2020, its Framework Programme for Research and Innovation.

        BRCCH Brochure

        Just over 2 years ago the University of Basel and ETH Zurich, with the support of Fondation Botnar, founded the BRCCH. The Centre hit the ground running and established its identity as a collaborative research center. With this brochure, the BRCCH presents further information and insight into itself and its research areas.

        Webinar: Insights Into COVID-19 Research

        Webinar: Insights Into
        COVID-19 Research

        The BRCCH invites you to join us online for free webinars on COVID-19.

        **Update September 17th, 2020 ** Thank you to everyone that attended our webinars in September! We had a great turnout-- in case you missed the presentations or you would like to watch them again, you can now stream them below or on our YouTube channel

          Description: The pandemic is placing the world in a stress test that is unprecedented. In response, organizations across sectors from research to nonprofit are mobilizing resources and taking action. This 3-part webinar series will highlight the BRCCH's ongoing collaborative research efforts in Switzerland, as well as dip into the global conversation about the current challenges and latest developments in the race to respond to the pandemic, with a focus on low- and middle-income countries.

          Sept 2nd & 9th: We will take an in-depth look into recently launched research projects focused on diagnostics and the immunology of COVID-19, as well as others focused on novel medical interventions for COVID-19. The projects are part of our recent Fast Track Initiative for COVID-19.

          Sept 16th: During the panel discussion, we will hear first hand from international experts about the current landscape of public health and how technology and partnerships spanning borders could meet current challenges in the pandemic.

          Register: closed. In case you missed the webinars, you can now watch them here (scroll down) or on our Youtube channel
          More: Download our programme below for info on the talks and speakers

          Banner image: Produced by the National Institute of Allergy and Infectious Diseases (NIAID), this highly magnified, digitally colorized transmission electron microscopic (TEM) image reveals ultrastructural details exhibited by three, spherical shaped, Middle East respiratory syndrome coronavirus (MERS-CoV) virions.

          Webinar Archive

          Prof Janos Vörös (ETH Zurich) & PD Dr Michael Osthoff (University Hospital Basel) present "A mobile, rapid diagnostic test system for COVID-19 based on lateral flow assays diagnosing SARS-CoV-2 infections at point-of-need," originally webcast on Sep 2nd, 2020.

           

          Prof Andreas Moor (ETH Zurich) presents "B cell immunity in convalescent COVID-19 patients with the aim of identifying high-affinity antibodies against SARS-CoV-2" originally webcast on Sep 2nd, 2020.

           

          Prof Melissa Penny (Swiss TPH) & Prof Roland Regoes (ETH Zurich) present "Modelling and machine learning to optimise medical interventions and health strategies for emergency response to the pandemic" originally webcast on Sep 9th, 2020.

           

          Prof Thomas Erb (University Children's Hospital Basel) & Prof Mirko Meboldt (ETH Zurich) present "The challenge of ventilation in the COVID-19 pandemic - improved patient care with low-cost ventilators based on novel integrated pressure sensors" originally webcast on Sep 9th, 2020.

           

          International Panel Discussion
          Prof Alain Labrique (Global mHealth Initiative, Johns Hopkins University) &
          Dr Solomzi Makohliso (EssentialTech, EPFL) &
          Prof Marcel Tanner (Swiss Academy of Sciences | Fondation Botnar)  &
          Akhona Tshangela (Africa Centres for Disease Control and Prevention) &
          Moderated by Dr Maxine Mackintosh (One HealthTech | The Alan Turing Institute)

          11 Projects for COVID-19 Research

          Fast Track Call (FTC) for
          Acute Global Health Challenges

          The BRCCH is pleased to announce 11 COVID-19 research consortia: The mandate of the BRCCH is to drive the development of innovative and step-changing health solutions for those who are most in need. With the support of Fondation Botnar, the BRCCH launches a new research initiative to address several critical areas related to the ongoing COVID-19 pandemic. The Initiative’s objective is to both enable research that will help mitigate medical and public health challenges in the short-term, and to also contribute solutions that will lead to better preparedness and reduced global disease burden in the long-term.

          The BRCCH Board approved the FTC external evaluation committee’s recommendation to support 11 projects that seek to deliver immediate impact in the following research areas:

            Rapid and effective consortia among BRCCH’s four partner institutions, University of Basel including University Hospital Basel (USB), ETH Zurich, University Children’s Hospital Basel (UKBB) and the Swiss Tropical and Public Health Institute (Swiss TPH), and in collaboration with research teams worldwide, will aim to address urgent health needs. The following projects start activities this month.

            Each project is considerably supported for a duration of 2.5 years.

            About the Call: The initial call for the FTC circulated on March 27th, 2020. 73 research consortia submitted project proposals on April 8th, with more than 97 (Co-) Investigators involved and total requested budget of approximately CHF 84 million. Applications were evaluated by an external and international panel of reviewers. The panel recommended to support 11 projects (success rate of 15%), which were subsequently approved by the BRCCH Board. The FTC initiative is generously supported by Fondation Botnar.

            Inaugural BRCCH Spotlight Day

            The inaugural Spotlight Day of the BRCCH marked the start of our initiative to build a community, both locally and globally, around the central mission of improving the health and well-being of children and adolescents worldwide. This event was an opportunity for local and international community to meet, start new dialogues and enable fruitful collaborations.

            More than 200 visitors joined the BRCCH at the inaugural Spotlight Day on January 30, 2020 – a great turnout to the Centre's first public event. After inspiring welcome addresses by Andrea Schenker-Wicki and Detlef Günther, four new BRCCH Multi-Investigator Projects showcased their vision for the next 5 years. Three international keynote speakers gave new perspectives on how research can be applied and translated. With this event, the BRCCH welcomed our new research projects at the Centre and the start of their research activities at the BRCCH.

            Watch a summary of the event:

             

            Artist Alex Hughes (Drawnalism) illustrated the event:

               

              The event programme:

              4 Projects Launch in Multi-Investigator Programme

              Multi-Investigator Programme (MIP)

              The BRCCH is pleased to announce its Multi-Investigator Programme (MIP) projects for the 2019 Call, which establish the first cornerstones of the Centre's research portfolio to improve the health and well-being of children and adolescents worldwide. MIP projects bring together researchers from its four partner institutions and therefore represent collaborative and multi-institutional research consortia.  
              The projects will start in early 2020 and will continue for five years. The Principal Investigators will introduce their projects on the inaugural Spotlight Day of the BRCCH on Thursday, 30 January 2020 at the Zentrum für Lehre und Forschung of the University Hospital Basel.

              The BRCCH supports the following Multi-Investigator Projects:

              Digital Support Systems to Improve Child Health and Development in Low-Income Settings
              In many low- and middle-income countries, families living in remote areas often have insufficient access to healthcare and health-related services to adequately support their children in the first years of their life. As a result, children’s early development is often delayed compared to children who grow up without such adversity, limiting their potential to lead a healthy and prosperous life. To address this, a new project led by Professor Günther Fink and Professor Daniel Mäusezahl will assess the extent to which a mobile phone-based interactive app can support the well-being of infants and young children growing up in low-and middle-income countries. Together with the creator of the app, Afinidata, the team will assess this platform through a study involving 2,400 families with young children in San Marcos province, Peru.  Through this study, the research team will not only learn about the potential reach and impact of the app, but will also collect feedback from local communities to further improve the app’s ability to support children’s healthy development.

                   Team members: Professor Günther Fink and Professor Daniel Mäusezahl from the Swiss Tropical and Public Health Institute from Swiss TPH, Professor Ce Zhang from ETH Zürich, Professor Stella Hartinger-Peña from the Cayetano Heredia University (UPCH), Professor Dana McCoy from the Harvard Graduate School of Education, and Andreana Castellanos, CEO of Afinidata.

              Burden-Reduced Cleft lip and palate Care and Healing
              Dr Andreas Mueller and Dr Barbara Solenthaler aim to simplify and optimize the surgical treatment of cleft lip and palate with the use of machine learning algorithms, smartphone-based images of the malformation, and 3D-printing of tailor-made palatal orthopedic plates. Not only will this project leverage on cutting-edge technology, but it will also aim to reduce the burden of surgery from a multi-step to a single-step procedure. The applicability of the proposed research project is especially relevant for children in low-income settings because current treatments are relatively high in cost and burdensome for the patient and his/her family which, in addition, may face challenges in securing the funding for the multiple surgeries presently needed. The project goals also allow the social reintegration of children with cleft lip and palate.
                   Team members: Dr Andreas Mueller from the University Hospital and University Children’s Hospital Basel, Dr Barbara Solenthaler from ETH Zurich, Dr Srinivas Gosla Reddy from GSR Institute of Craniofacial Surgery, Hyderabad, India, Dr Andrzej Brudnicki from the Institute of Mother and Child, Warsaw and Cleft Lip and Palate Clinic Formmed, Warsaw and Prof. Markus Gross from Disney Research.

              Living Microbial Diagnostics to Enable Individualized Child Health Interventions
              Malnutrition, infectious diseases and inflammatory conditions remain leading causes of illness in children living in low-and-middle income countries. In times of sickness and chronic illness, our gut microbes undergo genetic and physiological changes in response to the effects of insults such as infection or disease on the human body. Therefore, the monitoring of the changes in the gut microbiome has the potential to serve as a functional readout of the status of our health. In this project, the team led by Professor Randall Platt aims to develop a CRISPR-based technology involving engineered bacteria which are capable of sensing, remembering, and reporting on the environment within the gut. These bacteria will be utilized to provide an assessment of the nutritional, infection, and inflammation status of the gut and thereby provide a basis for individualizing and improving medical and lifestyle interventions for children and adolescents in the future.
                   Team members: Professor Randall Platt and Professor Uwe Sauer from ETH Zurich, Professor Dirk Bumann from the University of Basel and Professor Andrew Macpherson from the University of Bern.

              Precision Microbiota Engineering for Child Health
              From shortly after birth, the large intestine is colonized by billions of bacteria, which make up the intestinal microbiota. We are only just beginning to understand the extent and the mechanisms by which these bacteria influence child health and development. However, current studies support causal roles of these bacteria in diseases as diverse as allergy and autism. Despite this knowledge, we still have no accurate medical intervention to “fix” the microbiota. This project headed by Professor  Emma Wetter Slack develops novel tools to engineer the microbiota of individuals with inborn errors of metabolism or necrotizing enterocolitis: these conditions currently have high mortality rates, long-term consequences for child development and limited treatment options. The project aims to replace “bad” bacteria in the microbiome of the gut by “desirable” ones. This modification will be achieved with the help of engineered antibodies, and the direct targeting of individual genes in intestine-resident bacteria by employing CRISPR-Cas9 methodology. Moreover, since microbiota engineering can be applied across a wide range of childhood diseases, this effort has far-reaching implications for the future of medicine.
                   Team members: Professor Emma Wetter Slack, Professor Viola Vogel, Professor Ferdinand von Meyenn, Professor Johannes Bohacek, and Professor Shinichi Sunagawa from ETH Zürich, and Professor Médéric Diard from the University of Basel, Professor Matthias Baumgartner, Professor Johannes Häberle and Dr Sean Froese from the University Children’s Hospital Zürich, Dr Johannes Trück from the University Children’s Hospital Zürich and University of Zürich, Professor Giancarlo Natalucci from the University Hospital Zürich, Professor Christian Wolfrum from ETH Zürich, Dr Martin Behe from the Paul Scherrer Institute and Professor Adrian Egli from the University Hospital Basel.

              About the Call: The initial call for Multi-Investigator Projects circulated in Summer 2019. 28 applications were submitted, with more than 90 (co-) investigators involved and requested funding of approximately CHF 105 million. All submitted MIP applications were rigorously evaluated by an external and independent panel of reviewers. The first evaluation round was completed in September, the second round in October 2019. Applicants that  received positive assessments in both evaluation rounds were then invited to an interview-based workshop with our international Project Evaluation Board on 24 October 2019. On the basis of these presentations and all reviews, the evaluation board proposed four projects for funding, which the BRCCH Board accepted at its meeting on 6 December.

              Please see more information on the evaluation process. We look forward to promoting innovative and bold research projects for the health and well-being of children and adolescents worldwide!

              Archive Application Documents