Research Summary

Functional genomics of misfolding-induced stress response

Protein folding in the cell is complicated by parallel non-productive pathways that either lead to protein aggregation or protein degradation. Since misfolded proteins are toxic for cells, evolution has crafted mechanisms that sense the accumulation of misfolded proteins and respond by increasing the folding capacity of the cell.

Endoplasmic Reticulum (ER) is one of the organelles that is burdened by a high concentration of nascent polypeptides and is hence prone to misfolding-related problems. The most conserved sensor of misfolded protein accumulation in the ER is Ire1. This protein self-associates in response to accumulation of misfolded proteins in the ER and lead to downstream signalling known as Unfolded Protein Response (UPR).

Though our understanding of the downstream events emanating from the self-association of Ire1 is comprehensive, we do not understand the basis of Ire1 self-association and its regulation in presence of misfolded proteins. Main aim of my lab is to elucidate the players that assist Ire1 sense the accumulation of misfolded proteins in the ER and the molecular mechanism of this sensory mechanism. Techniques comprising of but not limited to, yeast genetics and protein biophysics, are being used to address the problem.

Figure Legend: Confocal image of Saccharomyces cerevisiae labelled with redox sensitive GFP targeted to endoplasmic reticulum