EAST LANSING, Mich. – Michigan State University (MSU) Department of Animal Science Assistant Professor Wen Huang is the recipient of a five-year, $1.6 million grant from the National Institute of General Medical Sciences (NIGMS) to study how variable DNA sequences affect the rate by which RNA is translated into functional proteins, and ultimately results in variation of quantitative characteristics of organisms.

By examining this fundamental process, Huang hopes to better predict quantitative outcomes of plants, animals and humans through genetic research by studying how efficiently organisms generate proteins, which are essential in producing specific traits. To achieve this, Huang’s research group is studying common fruit flies to examine how efficiently different strains of the insects translate messenger RNA (mRNA) into proteins.

Huang said previous research has been able to identify DNA variations that affect certain quantitative traits, but there remains a large gap between DNA and expression of quantitative traits. Quantitative traits, such as milk production in cows or disease risk in humans, are measurable phenotypes that depend on the cumulative actions of many genes and the environment.

“The information embedded in DNA has to be turned into mRNA and then proteins. These proteins interact with each other to carry out specific jobs,” said Huang, whose lab specializes in quantitative genetics and genomics, primarily in fruit flies and livestock animals. “There are a lot of missing links in between. What we're doing is trying to further fill in those links by looking at translation efficiency, something that has not been closely studied, and that we now have high throughput assays to measure them accurately.

“What we're looking to find is the differences in DNA sequence among individuals that make their translation efficiency different for each gene, and then once we know how these genes are translated in different individuals, we try to relate that difference to the quantitative trait variation observed at the organismal level.”

Huang’s lab will conduct three separate, but related experiments as part of the study. They will:

1. Examine genetic differences in translation efficiency in flies all from the same species.
2. Study genetic differences in translation efficiency between different fly species.
3. Use a massively parallel reporter assay that measures the effects of thousands of synthetic DNA sequences on translation in a single experiment.

“Next generation sequencing is a game changer,” Huang said of the massively parallel reporter assay. “When it came around about 15 years ago, people started to be very creative and develop new assays to utilize this high-throughput technology. What we hope to do here is to harness the power of it to help us quickly test how particular DNA pieces change translation efficiency.”

 “Once we can figure out the basic principles of a process with a model organism system, they can be applicable to real-world challenges. For example, personalized medicine, where we try to understand and utilize how the unique DNA sequence of a person can change their risk of developing a certain disease.”

Huang’s passion and his desire to do meaningful work with real-world impact have made this project a milestone in his research.

“We’ve been working on this research for a while now, and this grant allows us to extend this work in a more comprehensive way,” he said. “I have always been fascinated by how diverse nature is, and a lot of that is due to genetics.

“I have been very interested broadly in how DNA sequences will lead to differences in quantitative traits, which find applications in animal breeding and human health. I think that is a good combination where I can find my work useful in a context where I can make an impact in people’s lives and at the same time, it fulfills my scientific curiosity.”

Huang said he credits his MSU colleagues, including his mentors, animal science professors Jason Knott, Juan Steibel, and Mike VandeHaar and biochemistry professor David Arnosti for supporting him and helping him provide the foundation for his research to secure funding from NIGMS.