2023 Bioinformatics Outstanding Student Awards

Each year, the Georgia Tech Bioinformatics Graduate Program recognizes outstanding students at the PhD and MS levels. Each nominee was evaluated based on CV’s, transcripts, descriptions of their accomplishments, and letters of recommendation. An interdisciplinary committee of faculty members selected the winners.  Please join us in congratulating the following two outstanding students!

Deepali L. Kundnani, Ph.D. candidate, is the award winner of the 2023 Mark Borodovsky Prize for Excellence in Bioinformatics. Deepali joined the Bioinformatics Ph.D. program in Fall 2019. Deepali has been a tenacious and outstanding student that has a long list of accomplishments during her time at Georgia Tech. Deepali came to the program with an experimental background, however with little experience in computation. Being aware of the exponential learning curve, she had a goal to learn from the coursework as much as possible. Deepali’s hard work and dedication resulted in not only a perfect 4.0 GPA, but also gave her the confidence to develop an R package (FeatureCorr) that enables the use for detailed analysis of feature correlations from different sequencing-based technologies. That was published in 2021.

For as long as Deepali could remember, she wanted to work with novel and challenging problems in the field of biology and medical research, and being in the Storici Lab provided the opportunity to work on both aspects. Storici Lab studies incorporated ribonucleotide (building blocks of RNA) in genomic DNA, using lab developed ribose-seq method to obtain single-nucleotide resolution of embedded ribonucleoside monophosphate (rNMPs) of the ribonuclease (RNase) H2 enzyme (RNASEH2A, which initiate the removal of genome incorporated ribonucleotides) highly correlates with cancer proliferation markers and copy number alterations in cancer datasets suggested amplification of RNASEH2A gene in multiple cancers. Since then, Deepali worked on delineating various novel features of rNMPs like distribution and enrichment in different regions of the budding yeast and in the human genomes. Deepali’s Bioinformatics analyses in the DNA of yeast ortholog mutants of human RNase H2 defects associated with the neurological syndrome of Aicardi-Goutières (AGS) rrevealed unique features of rNMPs in these AGS mutants. The study is laying the groundwork to understand the biological and possible medical implications of RNA intrusions in human genomic DNA of cells carrying the RNASEH2A-G37S or RNASEH2C-R69W mutations of the AGS. This work is presented in the manuscript on “Distinct features of ribonucleotides within genomic DNA in Aicardi-Goutières syndrome (AGS)-ortholog mutants of Saccharomyces cerevisiae” by Kundnani et al., under review in iScience, and bioRxiv 2023. Additionally, Deepali developed creative computational solutions to overcome experimental limitations to filter high quality ribose-seq data that supported enhanced ribonucleotide signatures, such as hotspots and rNMPenriched zones in human mitochondrial DNA. The work and finding of this study are presented in the manuscript on “Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome” by Xu & Yang, Kundnani et al., Nucleic Acids Research in revision, and bioRxiv 2023. Further, she is working on studying correlation of different genomic and epigenomic activities with rNMPs found in the human nuclear genome using FeatureCorr, while profiling multiple cell lines to explore novel rNMP features. In Deepali’s Ph.D. journey she has also enjoyed mentoring students (M.S Bioinformatics & B.S. Biology) who have helped to validate novel ideas for investigation of rNMP-embedment properties.

In Deepali’s free time, she has enjoyed volunteering in departmental/school activities such as being a part of BINF t-shirt design committee, BINF Ph.D. orientation panel, MBM Cancer Seminar series committee to bring established researchers to Georgia Tech. Deepali has utilized her personal time to raise funds and awareness for mental wellness on campus by organizing and conducting breathwork and meditation workshops for Georgia Tech students and faculty, resulting in being nominated and selected for Emerging Leaders Advisory Board (ELAB) of Georgia Tech.

Vishva Natarajan entered Georgia Institute of Technology pursuing the 5-year BS Biology/ MS Bioinformatics program. Vishva is the recipient of the 2023 J. Leland Jackson Fellowship. Vishva was described by his Faculty Advisor, Dr. Matthew P. Torres, “as being one of the most talented graduate students that he ever trained, and I often use him as my primary example of how an exemplary student should perform”.

Vishva started working in Dr. Torres’ Proteomics lab as an undergraduate researcher, August 2022. He met Professor Torres in the Fall 2020 after enrolling in his special topics course in Proteomics: Technologies and Applications. Vishva brought in much enthusiasm and great potential to the lab, with his work ethic and his ability to work independently as a member of the team. Vishva has demonstrated a high aptitude for analytical biochemistry and bioinformatics. Dr. Torres was incredibly impressed with Vishva’s critical thinking skills, his high degree of self-motivation, and his experimental progress that made him a perfect candidate for this J. Leland Jackson Fellowship award.

Vishva’s independent research project was to investigate the effects of phosphorylation – a type of protein modification that naturally occurs in cells – on the ability of medical drugs to interact with their protein targets. This topic is of growing interest in the pharmacology community, especially to drug companies that attempt to understand fine-detail regulation of proteins to which they spend billions of dollars to target with small molecules. When the project began, the team didn’t have a target in mind. Vishva’s initial task was to conduct a bioinformatics analysis of drug targets and combine this will proteomics evidence for phosphorylation. Naturally, there were thousands of phosphorylation sites that he found on proteins that are known targets of drugs, and so Vishva had to think carefully about how to parse the data in a meaningful way that could highlight phosphorites of particular interest. After about one month of careful analysis and literature research, he came back with a tremendous discovery – that well known cancer target HIF2α (a transcription factor) undergoes regulatory phosphorylation at a site near its drug binding pocket – a fact that has been apparently overlooked by the research community. Vishva was rightfully intrigued by this and demonstrated to his advisor that there were several drugs used to target HIF2α in this pocket – many of which had crystal structures that could be used to conduct hi-resolution molecular dynamics simulations (seriously – Vishva discovered this on his own!).

Vishva proposed to analyze the potential effects of this phosphorylation at this site, T324, on the ability of HIF2α to interact with these drugs using Molecular Dynamics (MD) simulation. Phosphorylation of T324 in HIF2α was previously established as regulatory through its control of HIF2α dimerization with a MYC-interacting protein called SP1 that is important in cancer. However, how phosphorylation at this site affects HIF2α protein structure and small molecule interactions was unknown. Vishva homed in on a very interesting detail because of its high potential to impact human health and disease (this has always been a major driving force for Vishva as he is interested in both research and in medicine). Even more exciting is that a new crystal structure bound to the only FDA-approved HIF2α inhibitor, Belzutifan, was recently published in the middle of Vishva’s experiments. Smartly, he quickly moved over to simulate the effects of phosphorylation on this very important drug – finding that pT324 alters the affinity between Belzutifan and HIF2α – a discovery that is sure to have a major impact on the cancer community at large. To prove this, Vishva carried out a wide array of analyses including: 5 replicate long-time course MD simulations, dissection of the assembled MD trajectories enabling his discovery that phosphorylation promotes novel intramolecular interactions that disfavor stable interaction between HIF and Belzutifan, free-energy analysis that demonstrates statistically significant weaker binding between the two molecules, as well as exploitation of a novel machine learning model (produced by the Gumbart lab) that highlights critical residues in the interaction. Vishva has now written a full research article with high-quality figures that we will submit this Fall to the journal Molecular Pharmacology (the world’s premier journal in pharmacology that also published the recent Belzutifan/HIF structure). The title of his paper is: Dynamics of T324-phosphorylated HIF-2α:ARNT with FDAapproved antagonist Belzutifan.

In addition to Vishva’s outstanding Bioinformatics student recognition, he has won several other awards for his excellence in research. These include The John H. Ridley award for outstanding research by a pre-med student; the McCullum Undergraduate Research Scholar award; multiple President’s Undergraduate Research awards; as well as an award for Outstanding Undergraduate Teaching Assistant. In total he’s earned nearly $7K in funding through these and other smaller awards that he acquired in the last 2 years. Vishva goal after graduation is to attend medical school to combine his bioinformatics with patient care. He has been accepted to Medical College of Georgia, starting in August 2024. 

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Deepali Kundnani (PhD) and Vishva Natarajan (MS)
Deepali L. Kundnani, Ph.D. candidate
Vishva Natarajan, MS Bioinformatics
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Article Written by Sabrina Hall, Academic Program Coordinator.
For more information, contact Lisa Redding, lisa.redding@biosci.gatech.edu.

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