With a new low-cost method using mitochondrial proteins called VDAC, Indian Scientist finds a way to treat Cancer
Scientists are working on new methods of cancer treatment, which will remove and eliminate cancerous cells at an early stage of development. One such method is with the help of mitochondrial membrane proteins called Voltage-Dependent Anion Channels (VDACs) that control cell life and death. This removal and elimination (called apoptosis), if done at the early stages of cancer onset, will lower the financial burden on Indian society.
Dr. R. Mahalakshmi, Associate Professor, Indian Institute of Science Education and Research (IISER) Bhopal, a recipient of this year’s Swarna Jayanti Fellowship of the Department of Science & Technology (DST), Government of India, plans to identify molecular regulators that link mitochondrial VDAC proteins, which cell life and death (apoptosis), to cancer.
Three forms of VDAC exist in human mitochondria. Her research goals are directed towards identifying VDAC isoform-specific target sites that can be used for drug design and the development of effective medical interventions. Potent drugs targeting membrane proteins are exceedingly limited because these biomolecules are linked intricately with multiple indispensable functions in every cell. Particularly, mitochondrial membrane proteins undergo subtle changes in their regulation in several cancers. Hence, it has now become important to identify these subtle regulatory differences in these proteins under normal conditions and disease states.
By identifying differences between the different VDACs under normal conditions and disease states and characterizing these biomolecular differences, Dr. Mahalakshmi will generate ways to track and tackle cancer. Using information about molecular demarcating elements between these proteins, she will design and develop peptide-based targeted therapeutics that could inhibit mitochondrial membrane proteins in cancerous cells.
“My future research will additionally provide detailed insight on how cellular processes are regulated through mitochondria, and how the alterations in mitochondrial permeability during cancer impact other cellular processes like calcium balance, redox levels, and utilization of the energy produced by mitochondria. In addition to cancer, my work will also contribute to developing effective therapeutics for several neurodegenerative diseases,” Dr. Mahalakshmi pointed out.
In collaboration with pharmaceutical companies, Dr. Mahalakshmi envisions working towards customized therapeutics based on designed peptide-based mimetics of VDACs, as a direct outcome of the research.
“I strongly believe that promoting apoptosis at early stages of cancer onset is both advantageous and will lower the financial burden on Indian society. My research, and the development of peptidomimetic inhibitors, will lead to pharmacologically tractable solutions and effective medical interventions affordable by the Indian community,” she has said.
It may be noted that Prof. Mahalakshmi is one of the leading scientists in the world who is trying to solve the century-old protein-folding problem. Proteins of the same family are all folded the same way and they’re all stable to a similar extent, performing the same functions, she says. “The protein always does it right and it’s always an ensemble of identical structures with subtle differences.”
Today Mahalakshmi is an Associate professor in Biophysics, leading a team of researchers at IISER Bhopal, established in 2008 as a premier research institute in the state of Madhya Pradesh. “Considering how other universities and institutes worldwide are doing, I’d say it’s much better here. The entire concept of IISER is quite good and includes the opportunity for first-hand training in research for students.”
Transmembrane beta-barrels of the mitochondrial outer membrane are indispensable for cellular homeostasis. As these mitochondrial outer membrane proteins (mOMPs) play additional roles in ROS suppression, aging, cancer, and neurodegenerative diseases, Prof Mahalakshmi is now researching the biogenesis, function, and regulation of the three vital mOMPs:
(i) VDAC (Voltage-Dependent Anion Channel), the major metabolite governator
(ii) the Sorting and Assemby Machinery (SAM) its core protein Sam50, and its bacterial counterpart BamA
(iii) the Translocases of the Outer Membrane (TOM) complex, and its core unit Tom40.
The ultimate goal of the research in my laboratory is to identify a functional link between mitostasis, mOMP remodeling and quality control, and onset of cancer, neurodegeneration, and aging-associated diseases, she says.
Awards and Fellowships
The bright scientist has already bagged the following:
2019: Indian Peptide Society – Young Scientist Award.
2019: Exceptional Fellows Fund from Welcome Trust – DBT India Alliance.
2017 : SERB Women Excellence Award
2015 – Present: Wellcome Trust/ DBT India Alliance Intermediate Fellow
2014: NASI Young Scientist Platinum Jubilee Award, the National Academy of Sciences.
2014 – 2017: Associate, Indian Academy of Sciences.
2014: INSA Medal for Young Scientists, Indian National Science Academy.
2010 – 2015: Innovative Young Biotechnologist Award (IYBA) from the Department of Biotechnology, Govt. of India.
2010 – 2015: Ramalingaswami Fellowship.