About harmit

Harmit Malik is a scientist who runs a research lab at Fred Hutchinson Cancer Research Center in Seattle. Harmit grew up in Bombay, India (now Mumbai) in a family full of business people and engineers. As a kid, he spent his free time playing cricket in his neighborhood streets. When it came time to choose a career path, he started out following his family tradition and enrolled in a chemical engineering program for his undergraduate studies. However, after reading some science non-fiction books, he found himself getting increasingly interested in studying biology. Unfortunately, there was little time in his schedule to study biology and chemical engineering. Luckily for Harmit, a molecular biology professor agreed to tutor him in the afternoons after he taught his biology course, and Harmit was eventually admitted into a biology PhD program at Rochester University in New York.

What does he love about his job?

"My primary job is based on discovery. I love it because there have been many occasions where we, meaning some people in my lab, knew something that we had discovered, which no one else in the world knew. For someone whose primary motivation is curiosity, this is an amazing feeling."

One of the ways Harmit studies genetic competition is in the context of competition between humans and HIV (human immunodeficiency virus). Harmit takes an evolutionary approach to understanding why viruses like HIV are so deadly to humans--many of these human-virus interactions are the result of tens of millions of years of competition and constant "one-upping". According to Harmit, "In this genetic conflict, either the host is winning or the virus is winning" (Fred Hutchinson Cancer Research Center). To fight viruses, the human body makes proteins called restriction factors that can stop the virus from reproducing in our cells. However, viruses can respond with their own adaptations, and the battle continues.

The struggle between HIV and the human immune system is young in an evolutionary sense--it only arose in humans in the last hundred or so years. In that time, 25 million people have died from HIV-AIDS. HIV is part of a family of viruses, some of which (like the one scientists think HIV arose from) affect non-human primates like chimps, gorillas, and various kinds of monkeys. Because all primates (including humans) are closely related, we have a lot of similar genes and the proteins they code for. One of those, called TRIM5alpha, is for fighting viruses. In one species of monkey, the rhesus macaque, TRIM5alpha is very effective at stopping HIV in its tracks, and as such rhesus macaques are effectively immune to HIV. The human version of TRIM5alpha, however, seems to be losing in the evolutionary race against the virus.

In a recent study, a team of scientists including Harmit wanted to know why the human TRIM5alpha wasn't stopping HIV. One idea is that the human version of the protein is more "fragile" than in other primates. When a protein evolves, it is due to small, random changes in the DNA sequence of the gene that codes for it. Some of these changes can have very little impact on the overall function of the protein, and some can have negative impacts. The more "resilient" a protein is, the better it is at dealing with these neutral or negative changes until a very positive mutation comes along. If the human TRIM5alpha was "fragile" it's possible that small changes were making it unable to do its job.

To test this, the team Harmit was working with found a way to make many versions of human TRIM5alpha in the lab, all of which had different mutations in the part of the protein that is responsible for finding an attaching to the virus (the first step in eventually fighting it off). When they tested these different versions, they found that TRIM5alpha isn't fragile after all! Most of the mutations actually increased the protein's ability to fight HIV. One of their very promising findings was that human TRIM5alpha may only need a single mutation to be better at fighting HIV, and there are many possible mutations that fit the bill. They even found that, once TRIM5alpha gains one of those mutations, it doesn't easily lose them.

It's one thing to demonstrate this in the lab, but the human genome is complex and TRIM5alpha may not necessarily gain one of these positive mutations on its own. While Harmit's team showed that it's possible to "encourage" one of these mutations, gene therapy technology isn't advanced enough or safe enough currently to start applying these findings. The medical field has a ways to go before this information can be used to protect people from the devastating affects of HIV, but it is a very promising first step!