2020 CPB Pump Priming Grants

The Cambridge Centre for Physical Biology - Pump Priming Grants is an annual scheme aimed at generating new collaborations between early career research teams with complementary expertise, this way promoting multidisciplinary research in the field of physical biology in the University of Cambridge.

The CPB is pleased to announce that the winners of this year’s Pump Priming Grants are: Somenath Bakshi and Diana Fusco, Stephanie Höhn and Èlia Benito-Gutiérrez, and Georg Krainer and Jonathon Nixon-Abell. You can read about their projects below.

Somenath Bakshi (Engineering) and Diana Fusco (Physics) 

Title: Superresolution imaging of microbial biofilms using tunable synthetic genetic oscillators

In nature, bacteria often adhere to solid surfaces and create multicellular communities called biofilms. Formation of biofilms and their inherent resistance to antibiotics are at the root of many persistent and chronic bacterial infections. In order to develop effective therapeutics to prevent the formation or to promote the disintegration of these biofilms, we need to understand the structural aspect of the underlying microbial community and the communication systems that give rise to their defence mechanisms. Microbial biofilms are too thick for conventional microscopy techniques to peer into the underlying structure and organization of these communities. The signal-bleedthrough from neighbouring cells caused by diffraction of the optics reduces the contrast between cells in such tightly packed communities, making it very difficult to identify and track single cells in mature biofilms. To address this challenge, we are proposing to build a new superresolution imaging technique that identifies single cells in a biofilm using synthetic genetic circuits and 3D imaging techniques. We will combine the single-cell view of biofilms with biophysical growth models to analyse the spatial and temporal heterogeneities in the duplication rate of the biofilm at very high resolution, opening doors to investigate how a range of physical and biological mechanisms, e.g., mechanics, nutrient channel formation, quorum sensing, lead to different age architectures at different scales. By subsequently introducing an environmental change, e.g., antibiotic, we will then be able to monitor in vivo the emergence of resistance and the consequent re-arrangement of the biofilm as a function of these factors.

Stephanie Höhn (DAMPT) and Èlia Benito Gutiérrez (Zoology)

Title: How to get in shape - Multiscale mechanics of cell sheet folding

Understanding how cellular changes and tissue folding drive morphogenesis during embryogenesis is one of the biggest challenges of developmental biology. The goal of this project is to gain a mechanistic understanding of morphogenetic processes in three dimensions. Gastrulation is one of the most crucial steps in animal development. Invagination is the evolutionary basic form of gastrulation, occurring in cnidarians, echinoderms and cephalochordates, and plays an important role metazoan organogenesis (e.g. eye cup formation). Hence, gaining a mechanistic understanding of such a fundamental step in development is essential. Amphioxus (cephalochordates) occupies a pivotal phylogenetic position at the base of vertebrate evolution. The CPB Pump Priming Grant allows us to initiate studies on the mechanics of gastrulation in Amphioxus. Dr. Höhn has developed novel experimental and computational tools that enabled quantitative studies on cell sheet folding during inversion, a gastrulation-like process in the microalgal order Volvocales. These tools will be adapted to reveal mechanical tissue properties and their function during gastrulation. Dr. Benito-Gutierrez’ lab established methods to quantify morphology and gene expression in Amphioxus with single cell resolution. Together they will conduct the first biophysical studies on gastrulation in Amphioxus which will open up numerous research opportunities for comparative studies on the mechanics of morphogenesis.

Georg Krainer (Chemistry) and Jonathon Nixon-Abell (CIMR)

Title: High-throughput phase-state mapping of biomolecular condensates

Living organisms have evolved sophisticated mechanisms of intracellular organisation to spatiotemporally segregate biological processes. Traditionally, subcellular organisation has been associated with lipid-enclosed endomembranous organelles. However, recently, membraneless compartments, formed through liquid phase separation, have emerged as fundamental in organising and regulating cellular processes ranging from protein translation to metabolic homeostasis. These compartments, known as biomolecular condensates, are multicomponent structures comprising dynamic assemblies of proteins/nucleic acids, and are frequently associated with neurodegenerative disorders. In our project, we will develop a microfluidic-, optics- and omics-integrated approach to study the physical and functional properties of biomolecular condensates in a high-throughput manner. Our experimental pipeline will provide a framework for understanding the regulation of condensates and their constituents in the context of health and disease, and may provide a route for the development of diagnostics and therapies of currently untreatable neurodegenerative diseases and other pathological conditions.

The next call for CPB Pump Priming Grants will open in 2021. Deadline to be announced.