Invited Talk at Biotechnology on Drug Discovery, Heat Shock Proteins & Neglected Diseases
Dr. Utpal S.Tatu, Professor, Department of Biochemistry, Indian Institute of Science, Bengaluru
Malaria has been a problem in India for centuries. Details of this disease can be found even in the ancient Indian medical literature like the Atharva Veda and Charaka Samhita. Even in today’s era of modern life and urbanization, malaria remains as an existing threat in our society. Despite the research being done on the disease and efforts to eradicate it, Malaria is considered a “poor man’s” disease and pharmaceutical companies are more often than not, reluctant to involve themselves in investing their efforts on a drug that is not profitable to them.
Scientists like Dr. Tatu, have therefore focused their research to gain a better understanding of Malaria and the development of affordable therapeutics. As an established authority in the area of Proteomics, Dr. Tatu’s group at the Department of Biochemistry, Indian Institute of Science, is actively pursuing research to elucidate the mechanisms of molecular chaperones such as Hsp90 and its applications as a drug target for several neglected diseases.
Through a very interesting seminar, Dr. Tatu detailed the role of Hsp90 – a molecular chaperone that has housekeeping roles but is also induced under stress, when the HSF enters the nucleus and acts as a transcription factor for activating specific genes required to combat adverse conditions. A pertinent question that evolved from studies in the laboratory was – Do parasites depend on stress responses to remain virulent? In order for a parasite, such as the malaria-causing Plasmodium falciparum, to survive in the human host, it must be able to adjust to the increased temperature in the host’s micro-environment, which differs greatly from the temperature of the mosquito which is the parasite’s vector. Studies from Dr. Tatu’s laboratory clearly established that Hsp90 is responsible for the parasite’s survival. Therefore, a plausible anti-malarial drug could specifically target the Plasmodium Hsp90 (which differs biochemically from host Hsp90) and thus block the pathogenicity of the parasite. After extensive analysis of the Plasmodium Hsp90 in clinical samples using a variety of tools like Proteomics and Bioinformatics, the next objective is to carry out clinical studies to identify a potent anti-malarial drug.
This concept is not limited to a drug for curing only malaria. Technically, all parasites contain their own Hsp90 protein complex, which can be specifically targeted to hinder its infectivity. Examples of other parasites that are being analyzed include Trypanosoma brucei, and Giardia lamblia (where the Hsp90 is assembled in a very unique and fascinating manner). A similar treatment plan could be applied for Trypanosoma, the causative agent for Surra Disease which is commonly seen in animals in India and Africa, as well as Giardia which is a common cause of diarrhea.
Dr. Tatu’s visit proved to be an inspiration and a source of important information on current strategies for combating parasitic disease states.
A few of our M.Sc. students had the privilege of completing their project work in Dr. Tatu’s lab at I.I.Sc. Perhaps with continued collaboration between our campus and the Biochemistry department at IISc a new, affordable, drug against malaria can be synthesized using this methodology to save every malaria patient in our country from this malicious disease.
April 22, 2014
School of Biotechnology,Amritapuri