GEETA PALSULE
The Ohio State University , USA
Biography
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My rigorous academic training of 10 years followed by my original contributions in research have made me an expert in the fields of various aspects of biomedical research, focusing on, cell biology, genetics and molecular biology, biochemistry, and RNA biology. For my masters degrees I studied microbiology and molecular biology from University of Pune and from The Ohio State University. For my PhD I worked on transcription and RNA processing. I worked on a catalytic RNA called RNase P RNA, part of the housekeeping ribonucleoprotein complex (RNP) which is responsible for cleaving the 5'-leader from all pre-tRNAs. All tRNAs in the cell are generated with a leader at their 5' and 3' end which need to be removed for generation of a mature tRNA which can then take part in translation. This makes the function of RNase P essential in all domains of life. The ancestral eukaryotic RPR is a Pol III-regulated transcript generated with mature termini. In the branch of the arthropod lineage that led to the insects and crustaceans, however, a new allele arose in which RPR is embedded in an intron of a Pol II-regulated recipient gene and requires processing from the intron for maturation. I investigated the biogenesis mechanism for Drosophila RPR from its recipient intron. I found that intronic-RPR is processed from the excised intron to its active form by ancient nucleases that would have been present in the ancestor. Select proteins that act early in the RNase P enzyme assembly help prevent excessive nuclease trimming. Discovery of the RPR synthesis pathway casts light on events that happened ~500 million years ago when a new type of RPR gene was fixed. For my postdoctoral work, I continued research in RNA biology, expanding the work into human cells, induced pluripotent stem cells and induced neurons (iNs). I worked on how dysfunction of the RNA-degradation pathway is connected to some rare neurological disorders. Al-Raqad Syndrome is an ultra-rare autosomal recessive genetic disorder first reported in 2015. DNA sequencing of the patients revealed mutations in either of the two genes, DcpS and EDC3, and were presenting symptoms such as mild to severe intellectual disability, varying degree of motor neuron dysfunction, speech impairment and craniofacial deformities. DcpS (scavenger decapping enzyme) is responsible for m7G-cap structure hydrolysis after the RNA is degraded with the 3'-5' exosome mediated processing mechanism. To gain insights into the molecular mechanism(s), we in vitro generated induced neurons from patient lymphocyte-derived induced pluripotent stem cells. We observed defects in neurite outgrowth and neurogenesis which were corroborated with embryonic developmental defects observed in mouse disease models. I am currently working as a scientist in the cell and gene therapy research space in a leading biopharma company. I am working towards applying all my training and knowledge gained over the years to help in generating novel therapies in the rare disease space for the patients. </div>