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Dr Srinjan Basu

Dr Srinjan Basu

Group Leader in Stem Cell Science


Office Phone: +44 (0) 1223 746 961

Research Interests

We are interested in how chromatin binding proteins regulate genome architecture and gene expression during pluripotent 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 to gain insight into the role of key protein complexes involved in regulating poised genes during stem cell differentiation.

Collaborators

Prof Jenny Nichols (PDN)
Dr Thorsten Boroviak (PDN)
Dr Kevin Chalut (Dept. of Physics)
Dr David Klenerman (Dept. of Chemistry)
Prof Francis Stewart (TU Dresden)

Key Publications

Studying nuclear architecture at the single-cell level

Label-free live cell imaging of nucleic acids using stimulated Raman scattering (SRS) microscopy. Zhang X*, Roeffaers MBJ*, Basu S*, Daniele JR, Fu D, Freudiger CW, Holtom GR, Xie XS. ChemPhysChem 2012, 13(4): 1054-1059. PMC3516876

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy. Co-first author (*): Lu FK*, Basu S*, Igras V, Hoang MP, Ji M, Fu D, Holtom GR, Neel VA, Freudiger CW, Fisher DE, Xie XS. PNAS 2015, 112(37): 11624-11629. PMC4577158

Single cell studies of mouse embryonic stem cell (mESC) differentiation by electrical impedance measurements in a microfluidic device. Zhou Y, Basu S, Laue ED, Seshia AA. Biosensors and Bioelectronics 2016, 81: 249-258. PMC4833703

Combining fluorescence imaging with Hi-C to study 3D genome architecture of the same single cell. Lando D*, Basu S*, Stevens TJ*, Riddell A, Wohlfahrt K, Cao Y, Boucher W, Leeb M,Atkinson LP, Lee SF, et al. Nature Protocols 2017, 13(5): 1034.

3D structure of individual mammalian genomes studied by single cell Hi-C. Stevens TJ*, Lando D*, Basu S*, Atkinson LP, Cao Y, Lee SF, Leeb M, Wohlfahrt KJ, Boucher W, O’Shaughnessy-Kirwan A et al. Nature 2017, 544(7648): 59-64. PMC5385134

Imaging single proteins and protein complexes in live mammalian cells

Single-molecule imaging of transcription factor binding to DNA in live mammalian cells. Gebhardt JC, Suter DM, Roy R, Zhao ZW, Chapman AR, Basu S, Maniatis T, Xie XS. Nature Methods 2013, 10(5): 421-426. PMC3664538

The Nucleosome Remodeling and Deacetylase Complex NuRD is built from preformed catalytically active sub-modules. Zhang W, Aubert A, Gomez de Segura JM, Karuppasamy M, Basu S, Murthy AS, Diamante A, Drury TA, Balmer J, Cramard J et al. Journal of Molecular Biology 2016, 428: 2931–2942. PMC4942838

Studying the dynamics of chromatin-binding proteins in mammalian cells using single-molecule localisation microscopy. Basu S, Tan YL, Taylor EJR, Laue ED, Lee SF. Methods Mol Biol 2016, 1431: 235-263.

Three-dimensional Super-Resolution Imaging and Single-particle Tracking in Eukaryotic Cells Using a Double Helix Point Spread Function. Carr AR, Ponjavic A, Basu S, McColl J, Santos AM, Davis S, Laue ED, Klenerman D, Lee SF. Biophysical Journal 2017, 112(7): 1444-1454. PMC5390298

FRET enhanced photostability allows improved single-molecule tracking of proteins and protein complexes in live mammalian cells. Basu S*, Needham L-M*, Lando D, Taylor EJR, Wohlfahrt KJ, Shah D, Boucher W, Tan YL, Bates LE, Tkachenko O et al. Nature Communications 2018, 9(1): 2520. PMC6023872

Citrullination of HP1g chromodomain affects association to chromatin. Wiese M, Bannister A, Basu S(^), Boucher W, Wohlfahrt KJ, Christophorou MA, Nielsen ML, Klenerman D, Laue ED, Kouzarides T (^). Epigenetics and Chromatin 2019, 12 (1): 21. PMC6444592

Plain English

I develop single-cell and single-molecule imaging approaches to understand how poised genes are regulated during pluripotent stem cell renewal and differentiation in the early mouse embryo.