Laboratory of Molecular & Cellular Biology(LMCB)
We work in the field of cell biology. Our research interest is to understand the molecular mechanism of basic cellular processes such as dedifferentiation, neuritogenesis, migration, and cell division.
The molecular mechanism behind a carcinogen-induced tumor formation is not well understood. Using an in vitro model system, we demonstrated that C2C12- myotubes undergo fragmentation and generate mononucleated cells in the presence of 3-methylcholanthrene. These mononucleates can form colonies when they are seeded into soft agar. Fragmentation, the first step of dedifferentiation, which may arise due to loss of cytoskeletal structure, and the regulation of myogenic factor or cell cycle re-entry are independent processes [Saha et al (2011) and Dey et al (2013)].
Molecular motor protein, nonmuscle myosin IIs (NM IIs) are known to participate in neuritogenesis. But, how NM IIs play role in the neuritogenesis is not well documented. Saha et al (2013) established that neurite growth displays biphasic speed (retrograde phase with a negative CNL (change of neurite length per minute) value and protrusion phase with a positive value during neuritogenesis. Neurite’s length is dependent on the relative duration of the two phases. Also, earlier steps of neuritogenesis -step 1, sprouting, and step 2 formation of neurites-are interchangeable. The group has recently demonstrated that N-terminus region of C2 exon contributes towards neurite stability and neurite growth, because of its polar rich amino acids [Saha et al (2017)]. Whereas, NM II-A is required for neurite retraction and NM II-B for neurite growth.
During cellular migration, NM-IIs can act as molecular cue for different types of membrane protrusions in human breast tumor cell line, MCF-7. NM-IIA preferably induces blebbing whereas NMIIC1 lamellipodia in MCF-7 cells. In contrast, NM-IIB acts as a barrier for bleb formation. Mode of migration of a cell can be fine-tuned by the amount of each NM-II isoforms [Dey and Singh et al (2017)].
Actomyosin dynamics is involved in changing cell shape. We have established that Rho-ROCK-MLCK signaling axis phosphorylates NM II-A, resulting in stiffer cell cortex and providing a self-defense mechanism upon viral infection [Das et al (2015)].
With active collaboration with chemists and physicists, we have shown that siRNA-binding to its target mRNA is a stochastic resonance process, and expression of NM-II can be regulated by non-canonical miRNA [Ghosal S et al (2016), Chattoraj et al (2014)]. We are also involved in designing drug delivery system using naproxen-sodiums and its bioconjugate based hydrogel, and block copolymer based polymersomes [Majumder et al (2014), Dey et al (2013)].