Life Sciences & Biotechnology
Title : | Investigate the role of biomolecular condensates as protective reservoirs for the treatment of neurodegenerative diseases |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Neurobiology, Biomolecular Condensates |
Principal Investigator : | Dr. Soumit Sankar Mandal, Indian Institute of Science Education and Research (IISER), Tirupati, Andhra Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | soumit.mandal@iisertirupati.ac.in |
Equipments : | Inverted fluorescence microscope |
Details
Executive Summary : | Chaperone protein networks, such as hsp40, hsp60, hsp70, and small hsps, stabilize unstructured proteins in cells, preventing them from aggregating. However, under pathological conditions, proteins like intrinsically disordered proteins (IDPs) can form unstable proteins, leading to the formation of toxic amyloid fibrils. These proteins also undergo phase separation, forming viscous protein droplets that mature to form insoluble aggregates. These droplets can recruit drugs, peptides, or proteins, which can either accelerate or inhibit aggregation.
This proposal aims to investigate a strategy where protein droplets recruit and stabilize unstructured proteins in their monomer stage, preventing them from maturing to aggregates. Molecular chaperones, such as hsp40, have high affinity for unstructured proteins and can be used to generate protein condensates. The study will examine phase separation in the presence of macromolecular crowding agents and optimize protein and salt concentrations. The study will also monitor the recruitment of amyloid peptides into these condensates and their aggregation kinetics using Thioflavin T assay, turbidity assay based on spectroscopic techniques, and imaging using confocal microscopy (TEM). The aim is to investigate the role of protein condensates as gain-of-function reservoirs for storing amyloidogenic proteins and protecting cells from aberrant aggregation events. |
Total Budget (INR): | 66,73,832 |
Organizations involved