Research summary
Mitochondria, as we all studied in our school days, are bean shaped organelles considered as the powerhouse of the cell and the biochemical pathways leading to ATP synthesis within the mitochondria is well understood. However, studies in the recent past have established mitochondria as dynamic polymorphic structures having branched reticulate network interspersed with small bean shaped structures that integrate diverse extra and intra cellular signals to regulate several cellular functions.
Mitochondrial biology, therefore, has become a fast growing area in genetics and medicine, linking cell biological processes to metabolic disorders and cancer. We are interested in understanding the role of mitochondrion in controlling cell biological processes like proliferation, growth and differentiation. We use the model organism, Drosophila melanogaster, for genetic dissection of retrograde signaling pathways from mitochondria to nucleus that are essential in modulating cellular responses. Taking advantage of the advanced genetic tools available in this model system and using high-end microscopy and molecular genetic approaches we aim to unravel the mechanistic basis of mitochondrial regulation of cellular functions.
The other focus of our research involves embryonic stem cells. Embryonic stem cells, by virtue of their capacity to proliferate indefinitely and to differentiate into almost all types of somatic cells, hold the potential to be used for therapeutic purposes. Current research in this field aims to a) develop means to direct embryonic stem cells to differentiate into specific cell types that can be used for therapy and (b) to reprogram adult somatic cells to form induced pluripotent stem (IPS) cells. In this pursuit scientists are trying to understand the genetic regulations and modifications in the genome that contribute to the processes of reprogramming and differentiation. Although it is equally important to understand how these processes are affected by the cellular metabolic state, very limited studies address this issue. We aim to understand the metabolic control of pluripotency and early lineage specification of ESCs and EpiSCs. To achieve this goal, we employ a combination of microscopic, histological, biochemical, genetic and molecular cell biological approaches.
Selected Publications
- Freije, W.A., Mandal, S., and Banerjee, U. (2012). Expression profiling of attenuated mitochondrial function identifies retrograde signals in Drosophila. G3 2, 843-851.
- Mandal, S., Lindgren, A.G., Srivastava, A.S., Clark, A.T., and Banerjee, U. (2011). Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells. Stem cells 29, 486-495.
- Mandal, S., Freije, W.A., Guptan, P., and Banerjee, U. (2010). Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin- proteasome system. The Journal of cell biology 188, 473-479.
- Owusu-Ansah, E., Yavari, A., Mandal, S., and Banerjee, U. (2008). Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nature genetics 40, 356-361.
- Liao, T.S., Call, G.B., Guptan, P., Cespedes, A., Marshall, J., Yackle, K., Owusu- Ansah, E., Mandal, S., Fang, Q.A., Goodstein, G.L., et al. (2006). An efficient genetic screen in Drosophila to identify nuclear-encoded genes with mitochondrial function. Genetics 174, 525-533.
- Mandal, S., Guptan, P., Owusu-Ansah, E., and Banerjee, U. (2005). Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Developmental cell 9, 843-854.