Most of our tissues undergo constant wear and tear. A group of cells, known as the adult stem cells, continuously generate new cells that help our tissues regenerate and repair. In a population of stem cells, while some undergo cell division to self-renew their population, others differentiate to produce the specialized cells that make up a particular tissue. Maintenance of a balance between self-renewal and differentiation is crucial – bias towards self-renewal can cause cancer, and bias towards differentiation will result in the loss of stem cells. My laboratory investigates how this balance is achieved in the case of germline stem cells.
Germline stem cells (GSCs) serve as an experimentally-convenient model to study adult stem cell systems. Like the other types of adult stem cells, GSCs are capable of self-renewal and differentiation; they can either replenish themselves through mitosis, or undergo meiotic differentiation to produce the gametes egg and sperm. However, unlike the other adult stem cell populations, GSCs are readily available in genetically-tractable model organisms, such as the free-living nematode Caenorhabditis elegans. Therefore, we have chosen C. elegans GSCs as an adult stem cell model and investigate how these cells choose between mitotic and meiotic fates. This approach allows us to employ the various genetic and biochemical strategies available for the C. elegans animal model to studying adult stem cells. Since the process of mitotic and meiotic fate decisions have been conserved in evolution, we hope our discoveries will have implications in other organisms as well.
Currently, our work centres on the RNA-binding protein PUF-8, which belongs to the well-conserved PUF family of RNA regulators. PUF proteins control stem cell proliferation in diverse biological contexts in a number of species. Although these proteins have been predicted to regulate a large number of downstream mRNA targets, only a few have been demonstrated in the actual biological contexts. Recently, we have shown that PUF-8 functions redundantly with the GTPase-activating protein GAP-3 to promote meiotic differentiation by suppressing the signalling through the RAS / MAP kinase pathway. Whereas GAP-3 is known to inactivate RAS by promoting GTP hydrolysis, we found that PUF-8 suppresses the translation of the let-60 mRNA, which encodes the C. elegans ortholog of RAS.
- S. Vaid, M. Ariz, A. Chaturbedi, G. Anil Kumar, and K. Subramaniam 2013. PUF-8 negatively regulates RAS/MAPK signalling to promote differentiation of C. elegans germ cells. Development 140: 1645-1654.(PDF FILE)
- K. Pushpa, G. Anil Kumar, and K. Subramaniam 2013. PUF-8 and TCER-1 are essential for normal levels of several mRNAs in the C. elegans germline. Development 140: 1312-1320. (PDF FILE)
- S. Joseph, G. Gheysen and K. Subramaniam 2012. RNA interference in Pratylenchus coffeae: Knock down of Pc-pat-10 and Pc-unc-87 impedes migration. Mol and Biochem Parasit 186: 51-59.
- R. Mainpal, A. Priti and K. Subramaniam 2011. PUF-8 suppresses the somatic transcription factor PAL-1 expression in C. elegans germline stem cells. Dev Biol 360: 195-207. (PDF FILE)
- M. Ariz, M. Rana and K. Subramaniam 2009. C. elegans RNA-binding proteins PUF-8 and MEX-3 function redundantly to promote germline stem cell mitosis. Dev Biol 326: 295-304.(PDF FILE)
- S. Jadhav, M. Rana and K. Subramaniam 2008. Multiple maternal proteins coordinate to restrict the translation of C. elegans nanos-2 to primordial germ cells. Development 135: 1803-1812. (PDF FILE)
- B. C. Yadav, K. Veluthambi, and K. Subramaniam 2006. Host-generated double stranded RNA induces RNAi in plant-parasitic nematodes and protects the host from infection. Mol and Biochem Parasit 148: 219-222.
- I. D’Agostino, C. Merritt, P-L. Chen, G. Seydoux, K. Subramaniam 2006. Translational repression restricts expression of the C. elegans Nanos homolog NOS-2 to the embryonic germline. Dev Biol 292: 244-252.