We are an exclusive group with diverse yet overlapping interests. The research in lab revolves around the altered folding of proteins which leads to formation of ordered aggregates called amyloids. We utilize various biophysical, biochemical and microbiological tools to answer some of the fascinating questions pertaining to amyloids fibrils. The group is interested, but not limited to the following aspects of amyloids:
1. Understanding formation of microbial amyloids and their role in biofilm infections.
2. Development of strategies to combat amyloid-derived biofilm formation.
3. Cross-talk between human and bacterial amyloids and its potential role in neurodegenerative diseases.
4. Altered immune response to hetero amyloids.
Amyloids are highly stable ordered cross-β-sheet aggregates of proteins which are considered as the hallmark of neurodegenerative disorders like Parkinson’s and Alzheimer’s. Recent years have witnessed the emergence of a new class of amyloids designated as ‘functional amyloids’ where the amyloid fold is not deleterious to the cell, but is instead harnessed to perform diverse functions. Functional amyloids are produced by all cell types from microbes to human beings. A majority of the microbial amyloids play roles in surface adhesion (biofilm formation) and structural integrity and thus provide a fitness advantage. Often, these microbial amyloids play a key role in the progression of human diseases. We are interested in looking at amyloids that have both functional and disease-associated properties. We are initiating our research in the following directions:
Modulation of α-synuclein amyloid assembly by chaperone-like proteins
Most of the human proteins rarely but remarkably undergo spontaneous conformational change in response to genetic or environmental stimuli. α-Synuclein is one such protein that undergoes conformational switch resulting in amyloid formation that is linked to Parkinson’s Disease (PD) Progression. The present status of research on α-synuclein aggregation and PD progression reveals that the traditional therapy may not work to cure the disease in the long term.
There is dire need of new therapeutic interventions that can either prevent PD or suppress it at the earlier stage of progression. The role of innate chaperone-like proteins in circumventing α-synuclein amyloid assembly and their potential as future drugs is still in its infancy. Here, we plan to explore the anti-amyloid activity of chaperone-like proteins against synuclein aggregation. (Project funded through Early Career Research Award to Neha Jain by DST-SERB)
Role of microbial amyloids in neurodegenerative diseases
We are interested in understanding how bacterial amyloids influence the aggregation of human amyloids. We use a combination of biophysical techniques to elucidate the modulation of human α-synuclein amyloid assembly by bacterial amyloidogenic proteins. Currently, our experimental plan is limited to in vitro studies however in the future we will extend the study into cell culture and animal models.
Strategies to combat biofilm infection by targeting bacterial amyloids
Escherichia coli and related enteric bacteria form communities called biofilms that are resistant to host immune defenses and antibiotic treatment. Therefore, alternative approaches to conventional antibiotic therapy are urgently needed to treat biofilm related infections. The biofilm matrix is composed of exopolysaccharides, extracellular DNA and protein polymers commonly known as amyloid fibrils. Curli are amyloid fibrils produced in E. coli. The major subunit of the curli is CsgA protein that is capable of forming amyloid fibrils under in vitro conditions. An innovative strategy to prevent biofilm formation is to inhibit amyloid aggregation on the cell surface. We are putting our efforts in identifying and characterizing chaperone-like proteins that can inhibit amyloid and biofilm formation. (Project funded through Seed Grant to Neha Jain by IIT Jodhpur)