Research Interests

Toxic and beneficial outcome of protein aggregation inside cells

With the increasing life expectancy, developing effective treatments for numerous degenerative, age-related diseases becomes of enormous medical, social and economic relevance. Hence, research on cellular and organismal aging is now the focus of several leading laboratories and has provided different hypotheses about the causes of aging. One prominent hypothesis suggests that a gradual, age-dependent decline of protein homeostasis (proteostasis) accompanied by increasing protein-aggregation is the underlying cause of many age-related loss-of-function diseases. In our lab we perform systemic analysis of protein-aggregation in age-related proteostasis stress models. We are interested to identify the response of the cellular proteome against the newly triggered aggregates due to various stresses. Simultaneously, we investigate how components of the proteostasis network, including molecular chaperones, degradation machinery and others collaborate to maintain the integrity of the proteome in the face of protein-aggregation stresses. The specific questions include:

• Proteostatic control on protein-complex biogenesis!!
• Cellular response to protein aggregation!!

We use modern cell biology and state-of-the-art proteomics arsenal to address our questions.

Selected Publications

Widespread Nuclear Lamina injuries defeat proteostatic purposes of ?-Synuclein amyloid Inclusions. Mansuri S, Jain A, Singh R, Rawat S, Mondal D, Raychaudhuri S. J Cell Sci. 2024; doi: 10.1242/jcs.261935. Online ahead of print.

Increased supraorganization of respiratory complexes is a dynamic multistep remodelling in response to proteostasis stress. Rawat S, Ghosh S, Mondal D, Anusha V, Raychaudhuri S. J Cell Sci. 2020;133(18):jcs248492. doi: 10.1242/jcs.248492.

Aggregation of Respiratory Complex Subunits Marks the Onset of Proteotoxicity in Proteasome Inhibited Cells. Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S. J Mol Biol. 2019; 431(5):996-1015.

Interplay of Acetyltransferase EP300 and the Proteasome System in Regulating Heat Shock Transcription Factor 1. Raychaudhuri S, Loew C, Koerner R, Pinkert S, Theis M, Hayer-Hartl M, Buchholz F, Hartl FU. Cell. 2014; 156(5):975-85.

Firefly luciferase mutants as sensors of proteome stress. Gupta R, Kasturi P, Bracher A, Loew C, Zheng M, Villella A, Garza D, Hartl FU, Raychaudhuri S. Nature Methods. 2011; 8(10):879-84.