Mahita Jarjapu

Postdoctoral Researcher

Department of Computer Science, Dartmouth College

Contact: jmahita@gmail.com, mahita.jarjapu@dartmouth.edu

RESEARCH INTERESTS

The focus of my research lies at the interface of computational protein design, bioinformatics, computational chemistry/biophysics and immunology. I utilize various computational tools, leveraging experimental data obtained from sequencing of adaptive immune receptor (antibody) repertoires, to investigate antigen-antibody interactions.

In addition, I also work on designing protein therapeutics with improved stability and reduced immunogenicity by applying the principles of computational protein design.

My interest in this field first began during my Ph.D research when I applied the principles underlying protein structure and folding, computational chemistry, bioinformatics and biology to study protein interactions mediating cell signalling pathways. I integrated different computational approaches such as sequence analysis, structural modelling and molecular dynamics simulations to answer biological questions pertaining to protein-protein interactions that mediate the Toll-like receptor signalling pathway, a crucial component of innate immune signaling.

In particular, I was fascinated by how just a few amino acid mutations identified in human and mice could drastically affect TLR signalling. I studied the impact of these mutations at the protein structural level and used this information to predict how such mutations in the protein could alter the outcome of TLR signalling. I also performed high-throughput virtual screening to identify small-molecules that potentially disrupt specific protein-protein interactions within this signalling pathway.

Apart from working on TLR signalling-related proteins, I worked on next-generation sequencing of the genome and transcriptome of two medicinal plants, Ocimum tenuiflorum (Tulsi) and Moringa oleifera (Drumstick), as part of a multi-lab collaborative effort, to identify the genes responsible for conferring the characteristic medicinal properties on the plant. Our team developed a bioinformatics pipeline to enable structural and functional prediction of metabolic pathway enzymes in the sequenced genome/transcriptome.

Prior to starting my postdoctoral research, I also did a short stint in the design and chemical synthesis of peptides aimed at inhibiting Plasmodium falciparum merozoite invasion of erythrocytes.

RESEARCH EXPERIENCE

Postdoctoral Research Associate, Department of Computer Science, Dartmouth College,USA.

December 2018 - Present | Advisor: Prof. Chris Bailey-Kellogg

• Computational-guided epitope localization and binning of antibodies and repebodies from their respective repertoires-in collaboration with experimental research groups.

• Development of a computational pipeline to guide experimental de-aggregation and de-immunization of protein therapeutics-in collaboration with experimental research groups.

Short-term Visiting Researcher, TIFR Centre for Interdisciplinary Sciences, Hyderabad, India.

July 2018 - November 2018 | Advisor: Prof. Kalyaneshwar Mandal

• Analysis of protein-protein interactions involved in Plasmodium merozoite invasion of erythrocytes.

• Design and chemical synthesis of peptides for inhibiting merozoite invasion.

Bridging Postdoctoral Fellow, National Centre for Biological Sciences (NCBS), Bangalore, India.

April 2017 - June 2018 | Advisor: Prof. R. Sowdhamini

• Genomic and transcriptomic analysis of plants having medicinal value.

• Structural modeling and analysis of protein-protein interactions among select odoran-tbinding proteins present in mosquito-in collaboration with experimental research groups.

• Development of a computational pipeline to analyze protein-protein interactions in molecular dynamics trajectories.

• Prediction of cancer-causing fusion genes from RNA-seq data.

Ph.D Research Scholar, NCBS-TIFR, Bangalore, India.

August 2011 - April 2017 | Advisor: Prof. R. Sowdhamini

• Insights into TIR domain-mediated protein-protein interactions within the Toll-like receptor signalling pathways through various computational approaches.

M.Sc Student, Department of Chemistry, IIT-Madras, Chennai, India.

August 2010-April 2011 | Advisor: Prof. Nandita Madhavan

• Organic synthesis of a beta-turn mimic for the development of internally functionalized pores.

Trainee, Aurigene Discovery Technologies Ltd, Dr. Reddy’s Laboratories, Hyderabad,India.

May 2010 - July 2010 | Advisor: Dr. Vamsee Krishna, Medicinal Chemistry Division

• Trained in the synthesis, purification and mass spectrometric analyses of various intermediates used in the development of drugs.

PUBLICATIONS

Pasha, S. A,. Shafi ,K.M., Joshi, A. G., Meenakshi, I., Harini, K., Mahita, J., Sajeevan, R.S., et al., (2019). The transcriptome enables the identification of candidate genes behind medicinal value of Drumstick tree (Moringa oleifera)

2. Mahita, J and Sowdhamini, R. (2018). Probing subtle conformational changes induced by phosphorylation and point mutations in the TIR domains of TLR2 and TLR3

3. Mahita, J and Sowdhamini, R. (2018).Investigating the effect of key mutations on the conformational dynamics of toll-like receptor dimers through molecular dynamics simulations and protein structure networks

4. Mahita, J and Sowdhamini, R. (2017). Integrative modelling of TIR domain-containing adaptor molecule inducing interferon-β (TRIF) provides insights into its autoinhibited state

5. Mahita, J et al., (2015). An in silico approach towards the identification of novel inhibitors of the TLR-4 signaling pathway

6. Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties

7. Vaccination and immunization strategies to design Aedes aegypti salivary protein based subunit vaccine tackling Flavivirus infection

EDUCATION

Doctor of Philosophy (Biology), August 2011- August 2017, National Centre for Biological Sciences, TIFR, Bengaluru, India

Master of Science (Chemistry), 2009-2011, Indian Institute of Technology, Madras, Chennai,India

Bachelor of Sciences (Biological Sciences), 2006-2009, St. Francis College for Women, Hyderabad, India

SKILLS

Computational:

Computational-based sequence and structural analysis of proteins.
Computational protein design,protein structure modelling, protein-protein and protein-ligand docking, virtual screening of small molecules, and structure-based drug design, protein structure network analyses.
Performing long-length molecular dynamics simulations on clusters,
Working with high-performance computing clusters and Linux environment.
Programming in Python and R.
Genomic and transcriptomic analyses.

Experimental:

Basic cell and molecular biology techniques such as transfection, western blotting, immunofluorescence, confocal imaging, screening of small molecule inhibitors using cell line-based assays, cDNA synthesis, PCR.
Organic synthesis (solid phase and solution phase) of peptides, column chromatography, interpretation of 1D NMR spectra, HPLC-MS/MS spectrometry of peptides.

AWARDS AND HONOURS

Keystone Symposium Future of Science Scholarship, March 2017.
Travel Award, Department of Biotechnology, Government of India, March 2017.
Best Poster Presentation, NCBS Annual Talks, January 2015.
Best M.Sc Thesis Award, July 2011.
Council of Scientific and Industrial Research (CSIR)-NET, June 2011 All India Rank 57.

PERSONAL

I grew up and was educated in the Indian cities of Chennai, Hyderabad, and Bengaluru, all located in South India, before moving to Hanover for my postdoctoral research. I am an avid reader and like to dabble in multiple things including painting, blogging and dancing. I also maintain a blog at Chronicles of Life. During my graduate studies, I participated in a few dance performances organized by the Cultural Club of NCBS. A few videos of my dances can be found here.

I also volunteer as a science writer for The STEM Times, an Instagram page, that aims to convey complex scientific concepts in a simple manner to the general public.