Molecular Genetics Laboratory

tRNAs, translation, and diseases

Chronic diseases such as intellectual disability, diabetes, cancer etc., pose major public health care burden. Often, such disorders are a result of the continuous interaction between the genetic variability of individuals and the environmental factors. To develop better solutions for treatment and management of such diseases, it is essential to identify and characterize the regulatory circuitries that are impaired in such diseases. While genome-wide association studies (GWAS) studies are important to identify an association of alleles with disease conditions, a complementary approach is to characterize the mutations associated with rare genetic disorders that cause similar diseases.

Rare genetic disorders are devastating conditions caused mainly by recessive mutations. Identification and characterization of the regulatory circuitries impaired in such disorders may provide us insights into developing novel treatment strategies for related diseases. Mutations in tRNA modification machinery have been shown to be associated with several devastating diseases, ranging from intellectual disability to bronchial asthma and diabetes suggesting that tRNAs could be important in the aetiology of such diseases.

Using cutting-edge technologies, we focus on the characterization of gene regulatory circuitries impaired by mutations in tRNA biogenesis factors. We use brain-like, 3D cultures generated from embryonic stem cells (cerebral organoids) as our experimental system to elucidate the mechanisms by which mutations in tRNA biogenesis factors cause neurological disorders.

tRNA modifications are also known to be important for stress response in microorganisms such as bacteria and yeasts. We also extend our research into understanding how tRNA modifications play a role in shaping the host-pathogen interactions.