Research

Our Mission Statement
The mission of the laboratory is to exploit the advantages of zebrafish to dissect molecular mechanisms of gene function, regulation and genome organization in vertebrates.

Core Scientific Interests
Genetics, Developmental Biology and Genomics

Our present research interests are as follows:

1. Genetics & Developmental Biology 
Molecular mechanism underlying non-coding RNA mediated regulation of vascular and cardiovascular development in zebrafish.



Development of the vascular and cardiovascular system is a tightly regulated multistage process and zebrafish has been established as an excellent model for studying human vascular and cardiovascular biology. Importantly, the genetic programs that regulate the development of these important processes are conserved through evolution. Multiple protein coding genes and several non-protein coding genes have been known to be involved in the development and maintenance of the vascular and cardiovascular system. Work in our lab has established the biological role of several microRNAs in the development and maintenance of vascular integrity in zebrafish (Lalwani et al., 2012). 











The recently discovered novel class of long non-coding RNAs (lncRNAs) is also hypothesized to play crucial roles in regulating gene expression and thereby influence development of key biological processes (Bhartiya et al., 2012, Haque et al., 2014). We explored the dynamic expression landscape of lncRNAs in adult zebrafish and identified over 400 novel lncRNAs. LncRNAs with specific expression in the cardiovascular tissues of zebrafish were also identified (Kaushik et al., 2013).


We propose to systematically identify lncRNAs involved in the vascular and cardiovascular system development and maintenance. Further we propose to study the biological function and mechanism of selected lncRNAs involved in the development and maintenance of vascular and cardiovascular system employing reverse genetics approaches in zebrafish models. We would also potentially employ Locked Nucleic Acid enzyme (LNAzyme), Morpholino or TALEN based strategy for in vivo knockdown/knockout of selected lncRNAs in zebrafish embryos to understand their biological function (Suryawanshi et al 2012; Jalali et al 2013).



Using a conditional in vivo protein-trap mutagenesis system that reveals spatiotemporal protein expression dynamics we assess gene function in zebrafish (Clark et al., 2011). A sub set of the zebrafish in this forward genetics screen display specific cardiovascular and vascular phenotypes. These putative mutant zebrafish are templates for understanding new vascular and cardiovascular biology.












2. Functional Genomics 
Zebrafish models for rare genetic disorders- towards personalized and precision medicine in humans
(In collaboration with Dr. Vinod Scaria, IGIB)


We successfully sequenced the whole genome of a wild zebrafish, thus revealing the true extend of variation in this excellent model organism (Patowary et al., 2013). In parallel we also sequenced the first human genome in India (Patowary et al., 2012) and the first Malaysian personal human genome (Sallleh et al., 2013).

Currently we are deeply involved in the genome sequencing of human samples that are extremely healthy and those that are predisposed to rare genetic disorders. Once the rare human genetic variation is identified we propose to model the variation in zebrafish using genome editing technologies for functional validation studies. Thus zebrafish models for rare human genetic disorders enables personalized and precision medicine in humans. 

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