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January 14, 2020

Biozentrum is part of two BRCCH Multi-Investigator Projects

The research teams of Prof. Méderic Diard and Prof. Dirk Bumann at the Biozentrum of the University of Basel participate in two of four Multi-Investigator Projects which have been launched for the first time by the Botnar Research Centre for Child Health (BRCCH). Both projects are funded with a total of 8 Million Swiss Francs for the next four years.

 

Precision Microbiota Engineering for Child Health 

The project “Precision Microbiota Engineering for Child Health”, headed by Prof. Emma Wetter Slack of the ETH Zurich, aims to modify the microbiota of individuals with inborn errors of metabolism or necrotizing enterocolitis of the gut to improve the treatment options. Prof. Méderic Diard, infection biologist of the Biozentrum, University of Basel, is one of the research teams contributing to this research project.

By developing novel tools to engineer the microbiota of individuals the research teams aim 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 modulation of gene expression in intestine-resident bacteria by employing CRISPR-dCas9 technology. Since microbiota engineering can be applied across a wide range of childhood diseases, this effort has far-reaching implications for the future of medicine. 

Living Microbial Diagnostics to Enable Individualized Child Health Interventions

The project “Living Microbial Diagnostics to Enable Individualized Child Health Interventions”, headed by Prof. Randall Platt of the ETH-Department of Biosystems Science and Engineering (D-BSSE), aims to develop a CRISPR-based technology involving engineered bacteria which are capable of sensing, remembering, and reporting on the environment within the gut. Prof. Dirk Bumann, infection biologist of the Biozentrum, University of Basel, is one of the participating research teams. 

By monitoring the changes in the gut microbiome the researchers want to serve a functional readout of the status of our health. The CRISPR-based technology will use engineered bacteria which provide an assessment of the nutritional, infection, and inflammation status of the gut and can be a basis for individualizing and improving medical and lifestyle interventions for children and adolescents in the future. 

BRCCH Multi-Investigator Program 

In total, 28 applications were submitted in response to the first call for multi-investigator programmes (MIPs). The chosen projects are supposed to start within the first months of 2020. The Principal Investigators will present their projects on the inaugural Spotlight Day of the BRCCH on 30 January 2020, at the Zentrum für Lehre und Forschung of the University Hospital Basel. 

Botnar Research Centre for Child Health 

The Botnar Research Centre for Child Health (BRCCH) in Basel has been co-founded by the University of Basel and the ETH Zurich on 19 September 2018. The Centre is funded by a CHF 100 million contribution from the Fondation Botnar. The Centre brings together experts from basic research, engineering, translational science, clinical science as well as ethical, legal and economic experts to ensure the implementation of innovative healthcare solutions that can also be successfully applied in low- and middle-income countries.

Contact: Communications, Heike Sacher

T cells require the protein coronin 1 to reach and maintain their cell population size. The movie illustrates T cells dividing until their appropriate density has been reached, after which coronin 1 production reaches a plateau. As a result cell death (cells turning red) is initiated and T cells begin to die until the appropriate density has been reached again. Group Jean Pieters, Biozentrum; Animations: New Medium Center, University of Basel.

Maintenance of cell population size is fundamental to the proper functioning of multicellular organisms, yet the underlying mechanisms remain largely undefined. 

Coronin proteins are key regulators of cell population size 
All multicellular organisms require a mechanism to regulate the appropriate numbers of cells within their tissues and organs for optimal functioning. We basically ask the question: How do cells ‘tune’ their population sizes? Our long-standing interests in unravelling the function of coronin has recently defined members of the coronin protein family as key regulators of cell population size in a cell-intrinsic manner. 

How cells sense their population density
How cells sense their population density is largely unclear. The aim of our research is to analyze how coronin proteins orchestrate the processes involved in cell population size regulation and to delineate the molecular mechanisms involved.

An evolutionarily conserved pathway 
Coronin proteins are expressed in all multicellular eukaryotes, having evolved at the time of unicellular-to-multicellular transition. In our laboratory, we are using multiple approaches to delineate coronin-mediated cell population size regulation, ranging from analysis of facultative multicellular amoeba, to in vitro and in vivo analysis of the coronin signaling pathway in mammals, including mice and humans.

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