The Jain Lab studies how biomolecules in a cell self-organize. Specifically, they focus on how membrane-free cellular compartments like RNA granules form and function, and how these structures contribute to human disease.
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How do RNA molecules form aggregates in cells — a process that Jain has observed in some neurodegenerative diseases — and how can this be prevented?
During his postdoctoral research, Ankur Jain discovered that certain RNAs can form aggregates, clumping together and forming membraneless droplets or ‘gels.’ This process, known as phase separation, has been widely studied in proteins but not in RNA. He has found that RNA gels occur in, and could possibly contribute to, repeat expansion diseases, a set of neurological diseases including amyotrophic lateral sclerosis (ALS) and Huntington’s. Aberrant repetition of short sequences of nucleotides, the building blocks of DNA and RNA, is a hallmark of the genes associated with these diseases, and the RNAs containing these sequences are more likely to clump together. The Jain Lab is investigating the mechanisms by which cells prevent potentially deleterious RNA aggregation and will search for therapeutic agents that could one day safely dissolve RNA gels in patients.
RNA aggregation may also play a role in normal cellular function. Protein aggregation, a better-studied analogous process, is seen both in neurological disorders as well as in healthy cells. Phase-separated proteins mesh together to form barriers that help cloister and concentrate certain cellular processes. Jain hypothesizes that RNA gels may likewise help to compartmentalize cells and he is currently looking at instances of healthy RNA aggregation.
The lab is also investigating the role of RNA-DNA interactions in chromatin organization. There are instances of nucleotide repeats in our genome that occur even in the absence of repeat expansion disease genes. Repetitive DNA sequences at the end of our chromosomes interact with proteins to form our telomeres, structures critical for chromosome maintenance. They are studying the RNA transcribed from the telomeric sequences in order to understand both how they are structured and whether they undergo phase separation as seen in repeat expansion diseases.
Jain received his bachelor’s degree with honors in biotechnology and biochemical engineering from Indian Institute of Technology Kharagpur in 2007, and earned a doctorate in Biophysics and Computational Biology at University of Illinois, Urbana-Champaign, in 2013. He conducted his postdoctoral research in the lab of Ronald Vale at the University of California, San Francisco. In 2018, he became a Member of Whitehead Institute and an assistant professor of biology at the Massachusetts Institute of Technology.