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How our body recognises “foreigners”

Millions watched proudly as the armed forces of our nation displayed their mighty prowess for the world to see during the Republic Day parade. We regard those who protect our nation from foreign attacks with high esteem. Oddly enough, not many of us have stopped to marvel at the intricate mechanisms by which our human body has contrived a defense system no less admirable than the armed forces of our nation. A system that continues to protect us in spite of all that we throw at it.

Biologists call this “militant” unit of our body, the immune system. It has organs that produce cells to eat up bacteria, and other cells that generate molecules to attack ANY foreign body – the variety of objects it encounters and successfully overpowers, the sheer complexity of the system, is mind-boggling. And it is the intriguing facets of this system that Dr. Anjali Karande has dedicated 20odd years to decipher and exploit.

Dr Anjali Karande is a Professor at the Indian Institute of Science, where her research unit studies various aspects of how our immune system works. It is interesting how the human body is quite successfully able to recognize any particle that does not belong as “foreign”, and launch an attack against it. It is this “attack phase” that most of us recognize as “being sick”. For instance, when we develop a fever or rashes- it’s a sure sign of our body “attacking” the germs that are trying to get in.

But now here is an interesting thought - when women get pregnant with a tiny life growing inside them, that baby is half foreign. Basically, half the proteins in its body are the father's. Why isn't the mother's body attacking the growing baby that is quite obviously foreign? Here lies the beauty- the mother's body has a whole setup that is designed to protect the growing baby from her own immune system. And one of the many molecules that's assigned this role, is Glycodelin-A. This molecule is a protein with diverse functions; but most interestingly, it is present around the unborn baby and can make any cell that comes to attack the baby kill itself.

This function in particular is the object of Prof. Karande’s deepest scientific fascination. A large portion of her research efforts has been devoted to delineating the mechanism by which this molecule causes self destruction of the mother’s own "attacker cells" in its vicinity.

And she doesn’t stop there. She now has her students working on the mechanism by which this molecule could be exploited in transplantation therapies, where patients receive body parts from others when their own fails. “In most of such surgeries, the patients most inevitably show signs of their body rejecting the foreign organ, sometime later if not sooner”, says Prof. Karande.

This rejection is driven by the same group of cells that attempt to attack the growing baby. If we can engineer the molecule Glycodelin-A, to be expressed around the transplanted organ, then it should follow that it can induce death in any cell that comes to destroy the newly implanted organ. But the research is time consuming, explains Dr. Babita, a post doctorate fellow in her lab. Collecting miniscule amounts of amniotic fluid and then purifying the protein  is slow and laborious. But her enthusiasm while speaking the about project made it quite obvious that in this case, the end would justify the means.

But not everyone in the lab is working on Glycodelin-A. Meenakshi Sundaram for instance, a student of the undergraduate programme at IISc, is working on a toxin called Abrin. Extracted from the Ratti / Gunja plant, this molecule is highly toxic, even lethal. He is studying the molecule and trying to synthesize anti-Abrin molecules against it that could curb its activity.

“It is a highly lethal toxin and could be a weapon of choice for biowarfare. It never hurts to be prepared”, he explains quite animatedly. Its potency (less than 1/10 of a milligram of Abrin can kill a fully grown man) is what got Prof Karande interested in the first place. Having worked with this molecule for years and having recognized the mechanism by which it induces cellular death, she is not just interested in being able to synthesize "anti-Abrin molecules". She now wants to actually use this deadly molecule as a drug. Simply attach this toxin to another molecule which can recognize only cancer cells, and we have drug that can quite specifically destroy tumors. Of course, a few surrounding cells may also be lost in the process, but if we could get this to work, that's just a small loss in the bargain, she adds.

And all this is just a part of research focus of the Prof. Karande’s lab. With students working on various aspects of the diverse immune system, some trying to understand its basic mechanism, others trying to exploit their current understanding to design therapies, the studies give us a glimpse of the plethora of possibilities that currently define the field of immunology. From understanding the functioning of the organs and cells that are responsible for our protection, to designing “weapons” that can make the immune system comply to our every bidding, research at Prof. Karande’s lab is undoubtedly a thrilling endeavor, to say the least.

About the lab:

Anjali Karande is a Professor at the Department of Biochemistry, Indian Institute of Science, Bangalore. Web: http://biochem.iisc.ernet.in/anjalikarande.phpContact: Tel 080-22932306; Email anjali@biochem.iisc.ernet.in