Some diseases are characterised by the aggregation of peptides or proteins, and it is imperative to identify new targets for therapeutic intervention.
This is what inspired Sourav Ray, a researcher with the IITB-Monash Research Academy, to work on a project titled, ‘Aggregation of frog peptides: a model for amyloidogenesis’.
Amyloidogenesis is a polymerisation process in which soluble proteins misfold, or fold in a warped manner, explains Sourav. The main reason for this is amino acid mismatch in a protein sequence. This initiates the formation of soluble aggregates, and, eventually, insoluble, fibrillar amyloid.
Some peptides secreted by the Australian tree frog aggregate to form insoluble amyloid fibrils which are very similar to the deposits found in the brains of patients with Alzheimer’s (Image courtesy Wikipedia)
“Most animals have innate immune systems that comprise peptides. We have studied the peptides secreted from the Australian tree frog, and discovered that in addition to antimicrobial action there are also peptides that aggregate to form insoluble amyloid fibrils. These aggregates are very similar to the deposits found in the brains of patients with Alzheimer’s,” he adds excitedly.
Sourav plans to investigate the biophysical properties of the frog-aggregating peptide using molecular dynamics simulations and bioanalytical tools to provide an understanding of the aggregation process. “Small changes in the peptide sequence can prevent the aggregation of these peptides,” he says. “Hopefully, this will help in the design of new therapeutic targets for Alzheimer’s.”
Explaining the work he has done so far, Sourav says, “Most of the studies involving amyloidogenic peptides have been performed on fully-atomic systems. The major limitation in this approach is that a large number of atoms are involved, which require longer time scales to complete the simulation. We prefer coarse-grained or reduced atom models, as they help in speeding up the simulation process since fewer atoms are involved.”
The IITB-Monash Research Academy is a collaboration between India and Australia that endeavours to strengthen scientific relationships between the two countries. Graduate research scholars like Sourav study for a dually-badged PhD from both IIT Bombay and Monash University, spending time at both institutions to enrich their research experience.
Says Prof Murali Sastry, CEO of the Academy, “In a rapidly ageing world, understanding the origin of diseases such as Alzheimer’s would have tremendous impact. Sourav’s research work on the aggregation behaviour of peptides secreted by the Australian tree frog as a means of addressing Alzheimer’s underlines the truly interdisciplinary and multi-cultural nature of the IITB-Monash Research Academy PhD programme.”
Sourav—who has earlier undertaken short-term projects at National Institute of Virology (Pune), Institute of Genetic Engineering (Kolkata) and, Indian Biosciences Research Institute (Noida)—is working under the supervision of Prof Ajay Singh Panwar and Prof Lisa Martin.
Research scholar: Sourav Ray, IITB-Monash Research Academy
Project title: Aggregation of frog peptides: a model for amyloidogenesis
Supervisors: Prof Ajay Singh Panwar, Prof Lisa Martin
Contact details: firstname.lastname@example.org
This story was written by Mr Krishna Warrier based on inputs from the research student, his supervisors and IITB-Monash Research Academy. Copyright IITB-Monash Research Academy.