Cell Division, Intercellular Communication and Cellular Dynamics

Our research group is interested in illuminating the fundamental molecular mechanisms regulating cell division and intercellular communication, with the larger aim of elucidating their underlying impact on important biological processes.

Mammalian cells divide with a high degree of fidelity, ensured through tight molecular regulation of multiple pathways, to generate two daughter cells that contain the correct diploid complement of chromosomes. Elucidation of the molecular mechanisms of mitotic regulation is imperative to understand the basis for asymmetric stem cell division leading to differentiation, for understanding early development of multicellular organisms, as well as for potential therapeutic intervention in major diseases, prominently cancer and polycystic kidney disease.

We are studying molecular events controlling the metaphase to anaphase cell cycle transition, monitored by the Spindle Assembly Checkpoint, and dissecting the role of the ubiquitous molecular motor, cytoplasmic dynein, in regulating this process. We are also exploring molecular control of cytokinesis, the terminal step of mitosis, to understand the role of both molecular motors and vesicular traffic in ensuring completion of cell division.

Independently, we are probing the molecular basis for biogenesis and function of tunneling nanotubes - thin, tubular cytoplasmic connections between cells - a relatively newly discovered mode of intercellular communication seen in several eukaryotes. These structures play important roles in various physiological processes underlying health and disease, but the molecular mechanisms controlling their formation and function remain largely unresolved.

Our approach to answering the above questions is multi-pronged. We employ cell biological studies, high-resolution optical microscopy, biochemistry, proteomics, biophysical and structural biological approaches. In the future, we will collaboratively extend our studies to one or more model organisms, to understand the influence of intracellular molecular crosstalk in shaping the development and physiology of an organism.

We invite excellent recent PhDs in the life sciences (students who have recently submitted their PhD thesis are also welcome) to contact the PI directly for applying to prestigious postdoctoral fellowship opportunities. The lab has mentored competitive young postdoctoral fellows with similar/ complementary expertise as the lab, to enable them to progress to the next stage of their careers.

We invite excellent recent PhDs in the life sciences (students who have recently submitted their PhD thesis are also welcome) to contact the PI directly for applying to prestigious postdoctoral fellowship opportunities.

• Pushpa Kumari
  Wellcome-DBT Early Career Fellow
  pushpa@rcb.res.in
• Kuldeep Verma
  Young Investigator Awardee
  kuldeep@rcb.res.in
• Harsh Kumar
  Senior Research Fellow
  kharsh@rcb.res.in
• Pergu Rajaiah
  Senior Research Fellow
  pergu@rcb.res.in
• Amit Sharma
  Senior Research Fellow
  amit@rcb.res.in
• Amrita Kumari
  Senior Research Fellow
  amrita.kumari@rcb.res.in
• Sunayana Dagar
  Senior Research Fellow
  sunayana.dagar@rcb.res.in
• Chandan Kumar
  Senior Research Fellow
  chandan@rcb.res.in

• Dr. Megha Kumar (DST-INSPIRE faculty 2017-18; Young Investigator 2013-17)
  Current Position: DST-INSPIRE Faculty at the CSIR Centre for Cellular and Molecular Biology, Hyderabad India.
• Dr. Sharmishtha Samantaray (Young Investigator 2011-13)
  Current Position: Scientist III, Thermo Fisher Scientific, Bangalore India.

1. Kumar M, Mylavarapu SV (2017) Role of Dynein Light Intermediate Chains in Embryonic divisions and Vertebrate Embryogenesis Mechanisms of Development 145:S62
2. Mahale S, Kumar M, Sharma A, Babu A, Ranjan S, Sachidanandan C, Mylavarapu SV (2016) The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation.. Sci Rep 6:22
3. Mahale S P, Sharma A, Mylavarapu SV (2016) Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint. PLoS One 11:e0159646
4. Kumar M, Pushpa K, Mylavarapu SV (2015)  Splitting the cell, building the organism: Mechanisms of cell division in metazoan embryos IUBMB Life 67:575.
5. Sivaram MVS, Wadzinski TL, Redick SD, Manna T, Doxsey SJ. (2009) Dynein Light Intermediate Chain 1 is required for progress through the Spindle Assembly Checkpoint. EMBO J 28(7):902.
6. Srijita Banerjee, Mirsamadi N, Anantharaman L, Sivaram MVS, Gupta RB, Choudhury D, Roy RP. (2007) Electrostatic modification of the axial contact residues impact sickle hemoglobin polymerization by perturbing a network of coupled interactions. Protein J 26 (7):445.
7. Sivaram MVS, Furgason ML, Brewer DN, Munson M. (2006) The structure of the Exocyst subunit sec6p reveals a conserved architecture with diverse roles. Nature Structural and Molecular Biology 13(6):555.
8. Sivaram MVS, Saporita JA, Furgason ML, Boettcher AJ, Munson M. (2005) Dimerization of the Exocyst protein Sec6 and its interaction with the t-SNARE Sec9. Biochemistry 44(16):6302.
9. Sudha R, Anantharaman L, Sivaram MVS, Lohiya NK, Gupta RB, Roy RP. (2004) Linkage of interactions in sickle hemoglobin fiber assembly: inhibitory effect emanating from mutations in the AB region of the alpha-chain is annulled by a mutation at its EF corner. J Biol Chem 279 (19):20018.
10. Sivaram MVS, Sudha R, Roy RP. (2001) A role for the alpha 113 (GH1) amino acid residue in the polymerization of sickle hemoglobin. J Biol Chem 276(21):18209.
11. John MV, Parwez I, Sivaram MVS, Mehta S, Marwah N, Ali S. (1996) Analysis of VNTR loci in fish genomes using synthetic oligodeoxyribonucleotide probes. Gene 172:191.