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LAB STORY: Tiny proteins in the disease fighting arsenal

Consider the two life threatening diseases that made news recently: the Ebola outbreak last year and swine flu, which has been recurring since 2009. Strong evidence suggests that Ebola is transmitted by fruit bats, and swine flu by pigs. Both are “zoonotic” diseases – they are transmitted to humans from animals.

Could these epidemics have been prevented, if we had studied animal diseases more? We will never know. Prof Utpal Tatu, a Professor at the Department of Biochemistry, IISc is of the view that more research is needed into animal diseases. He operates under the idea of “One Health”: human and animal diseases cannot be viewed as separate entities in a complex world like ours.

“The “One Health” concept should be implemented in a developing country like India, where disease transmission is quick and easy”, he says.

In addition, he expresses concern over neglected diseases in Asia and Africa that severely hamper the health of the population, as pharmaceutical companies do not want to cater to the poorer section. Determination to find a way out of this complex situation and tackle the challenge of providing cost-effective cure has led Prof. Tatu and his team to orient their research towards realizing the mission of “One Health and Health for All”.

Fighting zoonotic diseases using tiny molecules

One of the ways in which Prof Tatu and his team study disease is by looking at proteins found in cells called “molecular chaperones”. When proteins are made in the cell, they need to be folded into a three-dimensional structure to function optimally. This is where chaperones come in – they can be thought of as “a friend in need”. They assist in proper protein folding. Moreover, they are most active in their assistance when the cells that synthesize them are subjected to stresses such as high temperature. Chaperones that act when temperatures are high are called “heat shock proteins”. The team showed that in times of disease, the heat shock proteins aiding the parasite could be our “friend indeed” too – they could serve as key targets for drugs.

Some heat shock proteins are found almost ubiquitously – in many organisms. Research from Prof Tatu’s lab has found that Hsp90, a heat shock protein is actively involved in sustaining diseases like malaria, surra and giardiasis. By identifying the different forms of Hsp90 in the parasites causing the above diseases, the researchers were able to successfully separate the parasite Hsp90s from human Hsp90.

The next step was to develop the parasite Hsp90s as potential targets for drug development. They found inhibitors that could bind with Hsp90 in the parasites and disable their function.

Translational research commenced in the lab, in the form of pre-clinical and large scale animal clinical trials, and were conducted successfully. The next stage of trials, by pharmaceutical companies, is being awaited. Positive results would open up an entire field of alternate drugs. This is especially important for malaria – the malarial parasite is developing resistance to the most commonly used drugs from the artemisinin family.

Success of the trials would also encourage more researchers to understand the value of one health and focus on controlling zoonotic diseases -- an action which would go a long way towards achieving good health in developing countries.

Omics in action

Omics studies involve information extraction by mining huge datasets. Each sub-discipline looks at all the genes in an organism, all the proteins produced by a cell or a micro-organism, and similarly all the metabolites produced: genomics, proteomics and metabolomics respectively. Their applications include helping distinguish between a normal and diseased cell, and analysis of diseases.

Using proteomics, Prof Tatu’s lab has investigated the proteome (all the proteins produced) by the malarial parasite Plasmodium vivax, for the first time ever. Among the 153 proteins detected, some that could be used as drug targets have been identified. Characterization of the other proteins also revealed potential vaccine candidates exclusive to P. vivax.

The research team's “One Health” approach for a better society is the first of its kind in India. Using the latest technologies and tools to find health solutions that are urgently needed to improve the health of developing countries is a challenge. The team's steadfast efforts to realizing this goal and the breakthroughs made so far should be a motivation to those involved in research.

Contact:

Prof Utpal S Tatu's homepage: http://biochem.iisc.ernet.in/utpaltatu.php

Email: tatu@biochem.iisc.ernet.in

Phone: +91-80-2293 2823