New Delhi, October 1: Scientists have developed a way to externally manipulate autophagy, the natural process through which cells remove and recycle damaged or unwanted material, potentially creating a new tool to study diseases such as cancer and Parkinson’s, according to a study.
The research was conducted by scientists from CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), the National Institute of Immunology, Ashoka University and the University of California, Los Angeles.
Autophagy is essentially the cell’s internal recycling system. During the process, unwanted cellular material is enclosed in a structure called an autophagosome, where it is broken down and its components are recycled for energy or other cellular functions.
Researchers studied the behaviour of a protein called LC3, which plays an important role in autophagy. Through computer simulations and laboratory experiments, they found that LC3 changes its shape when it interacts with the inner surface of the autophagosome.
The researchers then developed mutant forms of the protein that could either significantly increase or reduce autophagy. Their findings were published in the journal Nature Communications.
Potential Link to Cancer and Neurodegenerative Diseases
According to the researchers, the ability to control autophagy could help scientists better understand its role in diseases where the process becomes abnormal.
Autophagy can have different effects in cancer. It can help prevent tumour development by clearing damaged cellular material, but it can also help established cancer cells survive stressful conditions and potentially resist treatment.
In neurodegenerative diseases such as Parkinson’s and Alzheimer’s, impaired autophagy can contribute to the accumulation of toxic protein aggregates and damaged cellular components.
Study corresponding author Lipi Thukral, a computational biologist and senior principal scientist at CSIR-IGIB, said the findings suggest that autophagy could become an important target for future disease research.
She said that being able to switch the process up or down could allow researchers to observe its effects directly in cancer and Parkinson’s disease models.
The researchers have also filed international patents covering the engineered proteins and are exploring whether modified LC3 could eventually be delivered into cells using lipid nanoparticles.
Thukral said she is working with collaborators in Germany and the UK to investigate programmable autophagy in cancer cells and Parkinson’s disease.
Autophagy researcher Ravi Manjithaya of the Jawaharlal Nehru Centre for Advanced Scientific Research described the work as a major study combining computational modelling with structural, biochemical and cellular experiments.
He said the approach could be particularly relevant to neurodegenerative disorders in which misfolded proteins or damaged mitochondria accumulate inside cells.
The researchers stressed that the work is currently focused on understanding and manipulating the cellular process. Further studies will be required to determine whether the approach can eventually lead to safe and effective treatments.
The study highlights how combining computational biology, AI-based analysis and laboratory experiments could help researchers identify new mechanisms for studying complex diseases.
