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Dr Srinjan Basu

Basu Srinjan

        Dr Srinjan Basu

         Single-cell and single-molecule imaging approaches in stem cell biology

        Email: sb451@cam.ac.uk

        Laboratory: Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre

        Departmental Affiliation: Biochemistry 

Biography

Srinjan received his training in physics, chemistry and biology during a BA/MSci in Natural Sciences at the University of Cambridge and a PhD in Molecular, Cellular and Chemical Biology at Harvard University. He then returned to Cambridge and completed his postdoctoral research at the Department of Biochemistry. He is currently a Principal Investigator at the Wellcome-MRC Cambridge Stem Cell Institute.

During this time, he has developed several single-cell approaches:

(1) single-cell Hi-C to determine how the mouse genome folds into single cells,

(2) single-molecule imaging to track how single proteins and protein complexes assemble on chromatin, and

(3) label-free techniques to track stem cell differentiation in culture and to image dividing stem cells in living tissue.

He has since used some of these methods to gain insight into the role of NuRD (the nucleosome remodelling and deacetylase complex) in pluripotent stem cells. He is now developing approaches to study how other protein complexes regulate genome architecture during early mammalian development.

 

Basu research

Research

Our research focuses on developing single-cell and single-molecule imaging approaches to improve our understanding of stem cell renewal and differentiation.

In particular, we are interested in how chromatin binding proteins regulate genome architecture and gene expression during stem cell fate transitions and why they are often misregulated during early cancer progression. Single-cell approaches are key to understand how these proteins work due to the considerable cell heterogeneity that occurs during stem cell fate transitions.

In recent years, we have developed several biophysical and computational approaches to answer these questions. For example, we have established a method combining imaging and single-cell Hi-C to study genome architecture inside individual embryonic stem cells. To understand how proteins interact with each other and with chromatin, we have set up several in vitro and live-cell single-molecule imaging approaches capable of localising single proteins at <15 nm resolution.

We are continuing to develop novel single-cell and single-molecule imaging approaches but also using the techniques described above to gain insight into the role of key protein complexes involved in stem cell differentiation.

 

Plain English

Stem cells do not have a precise ‘job’ yet, but they can differentiate to become specialized cells, such as the ones that form our bones, our heart or our skin. Our research focuses on how stem cells transition into these different cell types.

In particular, we are interested in what happens to the DNA during these transitions. A molecule of DNA is over two meters long, and yet it can squeeze itself to fit inside the microscopic cells that form our bodies. This packaging process is not done randomly: in fact, a great number of proteins tend to the DNA to fold it into a precise 3D structure that will allow the cell to work properly. These molecules can also reshape the 3D folding in response to what a stem cell needs at any given moment, for example when it goes through differentiation.

When the proteins that fold DNA work incorrectly, it can often result in cancers or neurological disorders. Studying these molecules may therefore help us to develop better drugs or therapies for these conditions.

This is why we have developed methods to visualise these processes. For example, we created an approach that allows us to see for the first time how the entire mammalian genome folds inside a single stem cell. We have also built a microscope that lets us follow individual proteins ‘live’ as they fold the DNA in stem cells. Now we want to use these tools to look at what happens when the cells differentiate, and how folding errors could make them cancerous.

 

Key Publications