Mohan BALASUBRAMANIAN, Ph.D, Temasek Senior Investigator

Mohan Balasubramanian graduated in chemistry from Madras University in India and pursued a post-graduate program in microbiology and Biotechnology in Baroda, India.  He carried out his Doctoral research at the University of Saskatchewan, Canada, where he initiated his study of cell division in fission yeast.  Following post-doctoral research at Vanderbilt University, USA, where he furthered his study of cell division, he joined the Institute of Molecular Agrobiology Singapore in 1997 and the Temasek LifeSciences Laboratory Singapore in 2002.  Currently he is principal investigator of the cell division group as well as the deputy director, TLL.He is also a member of the Department of Biological Sciences at the National University of Singapore.

For information on PhD studies at TLL, click HERE

Visit the Mohan Lab's Website, click HERE

 

Click Here for Reagent Request

 

Research Interests

  • Cell Cycle Control
  • Cytokinesis
  • Mitosis
  • Morphogenesis
  • Cell Physiology
  • Yeast Genetics

Research Projects

My group is interested in understanding the mechanisms regulating the physical division of one cell into two. This process, referred to as cytokinesis, requires the function of an actomyosin based contractile ring in several organisms. We use the fission yeast Schizosaccharomyces pombe as a model to understand this process.
In fission yeast, the actomyosin ring is assembled at the medial cortex upon entry into mitosis and constricts upon mitotic exit. We are interested in understanding several questions relating to this process.
1. How is the actomyosin ring assembled starting from its constituents? 2. How is actomyosin ring constriction regulated? 3. How are the new membranes and cell wall assembled in coordination with actomyosin ring constriction? And 4. What are the cellular responses to a failure in cytokinesis? We are using a combination of several methodologies, including genetics, cell biology, functional genomic and biochemical approaches to answer these questions.

In the recent years, we have characterized a type II myosin important for cytokinesis. We have shown that the actomyosin ring is assembled from a myosin II containing progenitor spot. This spot is present throughout interphase and its components are incorporated into the actomyosin ring. Furthermore, we have shown by FRAP analysis that the myosin II progenitor undergoes minimal turnover and exchange of components, unlike the actomyosin ring, which undergoes dramatic turnover. To further understand this progenitor spot and its role in actomyosin ring assembly, we have purified myosin II associated proteins and identified several components by MALDI-TOF as well as ICAT approaches in collaboration with Rudi Abersold’s group (U Washington). We are currently further characterizing the components in order to understand the mechanism of actomyosin ring assembly.

We and others have recently made the discovery that components of the actomyosin ring turnover dramatically throughout the process of cytokinesis. We are attempting to understand if this observed turnover has a functional role.

We have made the discovery that lipid-raft like domains exist at the site of cytokinesis in fission yeast. We have also identified a novel protein Pal1p important for polarized growth during interphase and cytokinesis as well as Cps1p, a protein important for division septum assembly. We have also identified Cdc15p, a protein essential for cytokinesis, as a membrane component. We are trying to understand the role of lipid-rafts and other membrane domains in regulating cytokinesis via Cps1p, Cdc15p, and other proteins.

We have identified a second pathway for actomyosin ring assembly, which ensures cytokinesis is completed, upon mild damage to the cytokinetic apparatus. This actomyosin ring reassembly mechanism requires the function of a protein phosphatase Clp1p and the SIN, a conserved signaling network important for cytokinesis. This “cytokinesis checkpoint” ensures that the actomyosin ring is maintained for a prolonged period of time and also prevents mitotic entry of the two nuclei that are present in the same cytoplasm. In a functional genomics based approach, we have deleted all genes encoding protein kinases and have identified a protein kinase, Lsk1p, that is important for the maintenance of the actomyosin ring, in response to weak cytokinetic defects.

We believe these divergent studies will converge to generate a thorough appreciation of the spatial and temporal regulation of cytokinesis. These studies may also be applicable to related processes in other organisms.