Kabir H Biswas

Kabir-Biswas-portrait-2Senior Research Fellow, MBI

email: mbikhb@nus.edu.sg; kabir.biswas@live.com

website: Kabir H Biswas Research

RESEARCH AREAS
Cell signaling; Protein function regulation; Cell adhesion; Biomolecular assay development; Biochemistry; Biophysics; Cell Biology; Bioinformatics

RESEARCH INTERESTS
Dr. Biswas is interested in understanding mechanisms of cellular signal transduction mediated by cell membrane localized as well as cytosolic proteins. For instance, cells in a tissue receive both chemical (e.g. hormones or growth factors) as well as physical (e.g. mechanical tension or cell shape) cues that they need to appropriately process for both survival and growth of the whole organism. He believes that a comprehensive understanding of these processes in the cellular context will be useful in designing therapeutic strategies for alleviation of disease conditions.

BIOGRAPHY
Dr. Biswas joined the laboratory of Prof. Jay T. Groves at the Mechanobiology Institute (MBI), National University of Singapore (NUS) as Research Fellow in December 2011. He has developed assays for E-cadherin adhesion, signaling and crosstalk with other receptors using synthetic, micropatterned membranes and has uncovered a novel, nucleation-dependent mechanism of adhesion formation. Prior to coming to Singapore, he was an Integrated PhD (MS + PhD) student at the Indian Institute of Science (IISc), Bangalore and worked with Prof. Sandhya S. Visweswariah, Department of Molecular Reproduction, Development and Genetics (MRDG) towards his Masters as well as PhD thesis. There, he led a project that dealt on the possibility of multiple modes of allosteric regulation of proteins that are involved in cyclic-guanosine monophosphate (cGMP) signal transduction pathway such as guanylyl cyclases and cGMP phosphodiesterases.

E-cadherin junction formation involves an active kinetic nucleation process

biswas-fig-1Biswas KH, Hartman KL, Yu C-h, Harrison OJ, Song H, Smith AW, Huang WYC, Lin W-C, Guo Z, Padmanabhan A, Troyanovsky SM, Dustin ML, Shapiro L, Honig B, Zaidel-Bar R, Groves JT (2015) Proc Natl Acad Sci U S A 112(35):10932-7

A schematic representation of E-cadherin junction formation on a supported lipid bilayer. Cells seeded on a bilayer interact with E-cadherin by extending and retracting filopodia. Retracting filopodia increases the local concentration of interacting E-cadherin molecules on high viscosity, low mobility bilayers. This process most often fails on low viscosity, high mobility bilayers due to faster diffusive dissipation of E-cadherin molecules.

Distinct Allostery Induced in the Cyclic GMP-binding, Cyclin GMP-specific Phosphodiesterase (PDE5) by Cyclic GMP, Sildenafil and Metal Ions

biswas-fig-2Biswas KH and Visweswariah SS (2011) J Biol Chem 286(10):8545-54

Conformational transitions in PDE5. An ensemble of conformations of PDE5 can exist, with a spectrum of BRET, and the basal BRET being the average. Cyclic GMP selectively binds the low BRET conformers shifting the equilibrium toward reduced average BRET. Sildenafil induces conformational changes in the protein which require high activation energy resulting in a reduction in BRET. A change in the mean structure of the protein occurs in both the cases. Metal ions binding to the catalytic site alter the dynamics of the protein without causing any considerable change in the mean structure. Sequential binding of sildenafil and cGMP, and vice versa, further changes the mean structure of the protein, which for simplicity, is not depicted in the figure. Metal ion binding to the catalytic site reverts the cGMP-bound low BRET conformers to ~basal BRET conformers. In contrast, metal ion binding to the catalytic site enhances sildenafil-induced reduction in BRET.

PUBLICATIONS
Yu C-h, Rafiq NBM, Cao F, Zhou Y, Krishnasamy A, Biswas KH, Ravasio A, Chen Z, Wang Y-H, Kawauchi K, Jones GE, Sheetz MP Integrin-beta3 clusters recruitclathrin-mediated endocytic machinery in the absence of traction force Nature Communications 6:8672

Biswas KH, Hartman KL, Yu C-h, Harrison OJ, Song H, Smith AW, Huang WYC, Lin W-C, Guo Z, Padmanabhan A, Troyanovsky SM, Dustin ML, Shapiro L, Honig B, Zaidel-Bar R, Groves JT (2015) E-cadherin junction formation involves an active kinetic nucleation process Proc Natl Acad Sci U S A 112(35):10932-7

See also:
E-cadherin mobility regulates adhesion formation

Biswas KH*, Badireddy S, Rajendran A, Anand GS and Viswesweriah SS (2015) Cyclic nucleotide binding and structural changes in the isolated GAF domain of Anabaena adenylyl cyclase, CyaB2PeerJ 3:e882; DOI 10.7717/peerj.882

*Co-corresponding author

Finkerstrand T, Arshad N, Haukanes BI, Tronstad RR, Pham KDC, Johansson S, Havik B, Tonder SL, Levy SE, Brackman D, Boman H, Biswas KH, Apold J, Hovdenak N, Visweswariah SS and Knappskog PM (2012) Familial Diarrhea Syndrome Caused by an Activating GUCY2C Mutation N Engl J Med 366(17):1586-95

See also:
Familial diarrhea syndrome

Genetic mutation found in familial chronic diarrhea syndrome

Chromosome 12 Mutation Linked to Familial Diarrhea

GUCY2C gene mutation leads to familial diarrhea syndrome

Gene May Play Role in Frequent Diarrhea

Biswas KH and Visweswariah SS (2011) Distinct Allostery Induced in the Cyclic GMP-binding, Cyclin GMP-specific Phosphodiesterase (PDE5) by Cyclic GMP, Sildenafil and Metal Ions J Biol Chem 286(10):8545-54

Saha S, Biswas KH, Kondanapallic C, Isloor N and Visweswariah SS (2009) The Linker Region in Receptor Guanylyl Cyclases is a Key Regulatory Module: Mutational Analysis of Guanylyl Cyclase C J Biol Chem 284(40):27135-45

Biswas KH, Shenoy AR, Dutta A and Visweswariah SS (2009) The Evolution of Guanylyl Cyclases as Multidomain Proteins: Conserved Features of kinase-cyclase domain fusions J Mol Evol 68(6):587-602

Biswas KH, Sopory S and Visweswariah SS (2008) The GAF Domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) is a sensor and a sink for cGMP Biochemistry 47(11): 3534-43