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CCMB's strides in transgenics

V. Rishi Kumar

M. Somasekhar

IN THE quest for developing cost-effective and humane alternatives to using animals for scientific research, especially in drug discovery, researchers at the Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) have made a major breakthrough.

By developing a simple transgenic fly-Drosophila system, the CCMB has demonstrated a new method to screen and validate a class of drugs targeted against certain types of cancers.

The scientists have introduced a human colon cancer gene in the Drosophila, or fruit-fly's, system and expressed it. The transgenic system has been used as an in vivo assay, which means analysis can be done at the organism level. Interestingly, a large n umber of key regulatory genes are highly conserved between flies and humans, a feature that has been exploited by the scientist group.

The CCMB Director, Dr Lalji Singh, said with this development, the CCMB's transgenic fly system would be available for the use of pharma companies to validate potential drugs against cancer. This will also enable CCMB to take up projects of developing ne w drug screening systems for specific diseases, targets of interest to pharma companies.

Already, a US multinational and an Indian drug discovery company have asked the CCMB to validate some of their potential cancer drugs using the transgenic fly system. This has also been selected by the CSIR to validate some of the plant-derived bioactive molecules that have shown anti-cancer activities in cell culture studies.

Considering the high costs involved in using mice and other mammalian models, and with increasing awareness of animal rights and consequent restrictions and stringent procedures on the use of animals in experiments, it is important and logical to promote the use of alternative genetic model systems, he said.

Drs Singh and L. S. Sashidhara, the senior researcher associated with this work, said that "while bringing in savings in drug research for pharma companies, the fruit-fly system is one of the well-studied genetic systems. It also has a number of features , such as low cost of maintenance in laboratory and short life cycle. Also, transgenic flies can be generated with relative ease."

''Though fruit flies are immensely popular among scientists in many ways, this is the first time transgenic flies have been used specifically in drug validation,'' they said.

The CCMB scientists have generated genetically modified flies, which enable targeted expression of human genes in different genetic and physiological backgrounds. They have demonstrated that these transgenic flies constitute a novel, fast and inexpensive model system for studying the function of human protein and developing therapeutics for the prevention and treatment of cancer.

The development is a significant step in the role that such systems can play in functional genomics or understanding the function of specific genes in the human. The importance can be gauged, especially in the wake of the rapid rate at which human genes are being identified.

To strengthen research facilities in transgenics, an exclusive national centre is also being set up at the CCMB. Once the centre becomes operational, transgenic animals and experimental strains of mice will be available to Indian researchers trying to ge t a piece of action in the fast-paced developments in the genomics, drug discovery and biotechnology areas.

Transgenic mice and gene knock-out models of mice are the key drivers in most of the `hot' research in genetic engineering, basic biology and medicine across several laboratories in the developed countries. This facility will now be created at the CCMB, with an investment of Rs 2.5 crore by the Department of Science and Technology (DST).

Scientific research on these animals is being done to create models of human diseases. In the screening of bio-active molecules with potential to act as drugs, transgenic and knock-out mouse models are the preferred experimental tools.

The focus of the facility at the CCMB would be to seek applications of transgenic mice in drug discovery, development and commercialisation of new bioactive and traditional preparations, according to Dr Lalji Singh.

To be called The National Facility on Transgenic and Gene Knock-out Animals, the Centre will procure, maintain and breed animals and use them in understanding human diseases. Permission from the various regulatory bodies have been obtained for procuring the transgenic animals as well as the animal models, according to Dr Lalji Singh.

Some of the major diseases on which research would be done are Hepatitis B&C, Alzheimers, Parkinson's, Huntington's, Diabetes, Hypertension, Atherosclerosis, Breast and Colon cancers and Duchenne Muscular Dystrophy, Dr Lalji Singh said.

To house the new facility, an additional 800 sq. m. of animal space has been constructed on the first floor of the existing animal house of the CCMB. On the second floor, a laboratory complex of 800 sq. m. has been built to accommodate laboratories with facilities to do embryonic stem cell culture, cryo-preservation of embryos and micro-manipulation for animal surgery.

A dedicated molecular biology lab for conducting analysis of transgenic and knock-out mice and genetic monitoring of various strains of mice is also being put together. Scientists at the CCMB are already working on transgenic mice and gene knock-outs. Th ey have created a mouse lacking in specific gene from the mice embryonic stem cells. This novel strain of mouse lacking a gene would be useful in understanding the gene function.

With growing concerns on bio-terrorism following the recent anthrax attacks across the globe, the CCMB is set to establish a Rs 25-crore Biological Containment Laboratory near here on the Osmania University campus.

While the CSIR has agreed to provide funding of Rs 25 crore for the ambitious project, a one acre site is being acquired in the Osmania University campus, very close to the CCMB labs according to Dr Singh. At a meeting called by the Chief Minister, Mr N. Chandrababu Naidu, in the wake of anthrax threats in the State, the latter agreed to support this unique facility and get the necessary land allocated, Dr Singh said.