Research summary
- Glutathione, Sulphur and Redox have been one of the major interests of the lab. Glutathione is the predominant redox buffer in living cells, and is an unusual tripeptide that is made in the cell through non-ribosomal synthesis. Over the years we have discovered many enzymes and transporters in the glutathione and Sulphur pathways that has contributed to our understanding of how glutathione and redox homeostasis are maintained. The model systems that we use are yeasts.
- Currently our focus is on understanding how glutathione depletion and altered redox environments can regulate proteins and transporters and can play a role in signaling. We are also examining how the two major calcium channels that pump calcium into the cytosol can be controlled through redox by specific glutathionylation. In addition, we have been examining how under low glutathione conditions, secondary redox couples can become important, and are looking at some mitochondrial proteins that seem to influence these pathways. Enzymes in the Sulphur pathway such as MTHFR and the transporter cystinosin which have important roles in Sulphur homeostasis in mammals is also being studied in the lab- and we are looking at some novel aspects of these otherwise well studied proteins. We take a genetic, biochemical and molecular approach to tackling these different questions.
- A second interest in the lab is on the synthetic biology of isoprenoids. Here, we are engineering yeast to make specific terpenoids. We have also been taking up novel approaches to address the need to increase carbon flux into these pathways. In parallel, we are developing the molecular genetics of the red yeasts.
Selected Publications
- Chandel A, Bachhawat AK (2017). Redox regulation of the yeast voltage-gated Ca2+ channel homolog Cch1p by glutathionylation of specific cysteine residues. J Cell Sci. 130:2317-2328, 2017.
- Kaur A, Gautam R, Srivastava R, Chandel A, Kumar A, Karthikeyan,S * and Bachhawat AK* (2017) , ChaC2: An Enzyme for Slow Turnover of Cytosolic Glutathione. J. Biol Chem 292:638-651,2017
- Deshpande, A., Bhatia, M., Laxman, S* and Bachhawat, AK* ( 2017) Thiol trapping and metabolic redistribution of sulfur metabolites enable cells to overcome cysteine overload. Microbial Cell 4:112-126, 2017.
- Wadhwa, M. and Bachhawat, A.K.* (2016). A genetic screen for increasing metabolic flux in the isoprenoid pathway of Saccharomyces cerevisiae: Isolation of SPT15 mutants using the screen. Metabolic Engineering Communications, Volume 3, 164–172, 2016.
- Kumar A, Tikoo S, Maity S, Sengupta S, Sengupta S, Kaur A, Bachhawat AK.*. (2012) Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione.EMBO Rep. 13:1095-101.
Group