VIRUS - HOST INTERACTIONS

We study the role of regulatory RNA elements in transcription and translation control of viral RNA.
 
In HIV, we study the interactions of host proteins with the 5'-UTR in the viral mRNA to initiate cap-dependent translation of HIV proteins. We also study how HIV hijacks the transcriptional machinery to make multiple copies of its genome during productive viral replication.
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In Arenaviruses, such as Lassa, that cause lethal haemorrhagic fever diseases, we study the interaction of intergenic regions with host and virus proteins. Recombinant intergenic regions have been shown to attenuate the virus and thus are promising candidates for development of pan-arena virus vaccines. However, exact mechanism is unknown. 

RNA MISFOLDING PATHOLOGIES

RNA misfolding is the pathological cause of several classes of neurological disorders such as myotonic dystrophy (DM), fragile X syndrome, Huntington’s, ALS/FTD, etc. Understanding the structure-function relationship of such misfolded RNA is thus essential for comprehending the molecular mechanisms of these diseases, and for developing new RNA-based therapies.  We thus use multidisciplinary approach involving cell biology, various microscopy techniques, and structural biology to investigate the structure and interactions of RNA in situ.

CHALLENGE-DRIVEN METHOD DEVELOPMENT

RNA and their protein complexes are one of the most challenging systems to study using structural biology techniques. Thus, we develop methods integrating Mass Spectrometry, Cryo-EM and molecular simulations to build capacity for elucidating RNA structure and dynamics. 

We have pioneered OrbiSIMS guided structural modelling of native RNAs, affinity based approaches for cryo-EM sample preparation and NMR-restrained simulations of RNA.