“Harmit’s work requires a multi-disciplinary approach and he nimbly moves between organisms and techniques to address whatever mechanism is at the root of a genetic conflict,” said Basic Sciences Director, fellow HHMI Investigator and previous Novitski Prize winner Dr Sue Biggins.
Malik first became interested in genetic conflict during his postdoctoral training in the laboratory of Hutch geneticist Dr. Steve Henikoff. He wanted to understand why centromeres — key segments of chromosomes that are required for proper separation of chromosomes during cell division — are evolving rapidly. Usually such fundamental stretches of DNA evolve slowly.
Like Novitski, Malik used fruit flies to untangle the mystery. With Henikoff and others in the lab, Malik proposed the centromere drive hypothesis, theorizing that centromeres are engaged in their own molecular arms race with the specialized proteins that bind that region of DNA. Since then, Malik has shown that rapid evolution of centromeric DNA and centromeric proteins can lead to reproductive isolation — the inability to successfully produce offspring — between emerging species and result in defective cell division.
“This paradigm-shifting model triggered scores of discoveries in flies, plants, mammals, and fungus that reveal the pervasiveness of rapid centromere protein evolution as well as the mechanistic details of how selfish centromeres hijack meiosis,” said University of Pennsylvania geneticist Dr. Mia Levin, who trained with Malik.
With fellow Hutch geneticist Dr. Michael Emerman, Malik pioneered the field of paleovirology. He pioneered the idea of “evolutionary echoes” — the traces of long-past viral infections that left their mark in a species’ anti-viral genes — to infer the evolutionary influence of ancient, extinct viruses. His paleovirology strategies allow Malik to date ancient viral infections and trace the evolution of host antiviral genes to predict how susceptible a modern species may be to an infection. Using evolution as their guide, Malik and Emerman have tweaked antiviral proteins to improve potency while maintaining the breadth of viruses they protect against, which could help scientists working to develop better therapies against HIV.
“Harmit has a remarkable ability to identify the most interesting phenomena and discover new evolutionary mechanisms that others have overlooked,” Biggins said.
Malik’s ability to look at old problems with a fresh perspective is one of his secrets, said Henikoff, also an HHMI Investigator.
“Something that I think has a lot to do with his incredible success is that he has the uncanny ability to explain to you what you thought you already knew,” Henikoff said.
An inspiration beyond the bench
It’s not merely Malik’s creativity and scientific advances that set him apart, his colleagues said.
“Harmit has had a catalyzing effect on the division,” Biggins said.
Malik makes time to help junior faculty by reading and critiquing manuscripts and grant proposals. He helped found a postdoc boot camp, in which postdocs write sample job applications and practice their job and chalk talks in preparation for seeking their first faculty positions. Malik is involved at every step, from evaluating proposals to giving feedback on the participants’ presentations.
“It’s amazing that Harmit can accomplish so much in his own science and still have time to give so much to help others’ in their careers,” Biggins said.
The scientists lucky enough to train in his lab find Malik’s mentorship invaluable and inspiring.
“Talking science with Harmit is invigorating and joyful in part because of his openness, his authenticity, and his humility,” Levin said. “He is a perpetual student, making these conversations feel like one of collaborative discovery. These interactions help you see the gold that you are sitting on and give you the confidence to tell the world about it.”
Malik’s wide-ranging interest, never limited to a single species or question, is a secret of his success, Biggins said.
“Part of his success in training is helping people identify the genetic conflict in what they care about, so they can run with it,” she said. “Harmit deserves as many awards as he can get.”