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College Stories: Nitin Phadnis

Nitin Phandis

CoS Award for Fostering Undergraduate Research Excellence 

The CoS Award for Fostering Undergraduate Research Excellence recognizes excellence in fostering undergraduate research and promoting experiential learning during the academic year. This year, we express our appreciation to two faculty members with outstanding record of mentoring and advancing undergraduate research:

Nitin Phadnis, Assistant Professor, School of Biological Sciences
Tino Nyawelo, Assistant Professor (Lecturer), Physics and Astronomy


Nitin Phandis

Solving the “Mystery of Mysteries”

Discover Magazine  - 2017 

Question: How – and why – do new species evolve? What drives the splitting of one species into two different species?

“Our genomes, instead of being static entities, are dynamic conglomerates of genes that are in evolutionary conflict with each other. These evolutionary conflicts within the genome are a driving force in the formation of new species,” says Nitin Phadnis, an Assistant Professor of Biology at the U.

Phadnis is trying to solve a genetics puzzle that has eluded scientists, and philosophers, for nearly two centuries – how do two species evolve from one species?

Research in his laboratory uses a unique combination of classical genetics, DNA sequencing (genomics) and cell biological techniques to answer this question in various species of fruit flies.

It is well known that speciation, the process by which a species splits itself into two, involves the evolution of reproductive isolating barriers such as the sterility or inviability of hybrids between certain types of populations.

And yet, in his masterpiece, “On the Origin of Species,” Darwin could not find a satisfactory solution to the apparent paradox of why natural selection would allow the evolution of detrimental traits such as sterility and inviability that diminish the chances of successful reproduction. Darwin termed this problem the “mystery of mysteries. ” The problem is one of the most important and unanswered questions in biological research over the past 150 years.

In 2015, Phadnis led a University of Utah study that identified a long-sought “hybrid inviability gene” responsible for dead or infertile offspring when two species of fruit flies mate. The discovery shed light on the genetic and molecular processes leading to the formation of new species, and could also provide clues to how cancer develops.

“We knew for decades that something like this gene ought to exist, and our approach finally allowed us to identify it,” says Phadnis.

To circumvent traditional roadblocks to identifying speciation genes, his laboratory devised a novel strategy centered on reversing hybrid incompatibilities that involved chemical mutagenesis, hybrid rescue, and sequencing of whole genomes. The results were published in the journal Science in December 2015.

FUNDING
In 2013, when Phadnis joined the Biology faculty, he was appointed as the Mario Capecchi Endowed Chair in Biology. The position provided $40,000 per year for four years to support his early research efforts at the U.

Work in the Phadnis laboratory is supported by a National Institutes of Health grant titled, “The molecular basis of speciation in Drosophila.” It provides nearly $1.5 million over five years. Another proposal, “The genetic basis and molecular mechanisms of segregation distortion,” is pending at the National Science Foundation and could provide more than $1.5 million over five years.

In 2016, Phadnis was named a Pew Biomedical Scholar – one of just 22 in the country to be selected that year. The accolade provides $75,000 per year until 2020.

“The Pew Scholars Program in the Biomedical Sciences provides funding to young investigators of outstanding promise in science relevant to the advancement of human health,” according to the Pew website.

IMPACT
Scientific studies are providing new perspectives to fundamental cellular processes that are important in cancer biology and birth defects in humans.

In particular, Phadnis’s work is revealing novel insights into the mechanisms of DNA-damage induced cell cycle “checkpoints” and the consequences of chromosomal breakage. These processes are fundamentally important in the causes of fighting cancer.

Phadnis also is studying certain chromosomes known as “segregation distorters” that are critical in understanding problems that can lead to infertility or birth defects. These enigmatic elements, which work by violating Mendel’s Laws, are ubiquitous in nature and are a potent evolutionary force in influencingthe structures of genomes.

FUTURE
Advances in whole-genome sequencing technologies and population genetic methods to detect selection in genome-widestudies have revealed several classes of genes that evolve rapidly under positive selection.

“We have found rapid evolution driven by positive selection in interesting classes of genes, such as genes involved in meiosis, nuclear transport, and RNA interference,” says Phadnis. “We are interestedin understanding the causes of rapid evolution at these genes, and the consequences of functional divergence.”

Collectively, these research projects are helping unravel Darwin’s “mystery of mysteries” by informing the molecular and functional basis of speciation and by guiding the investigation of fundamental evolutionary processes that shape the complexity of genomes, cells, and species.

Last Updated: 4/11/19