Lusk’s two-year award for just over $55,000 is an individual postdoctoral fellow award named after Ruth L. Kirschstein. Lusk works in the lab of his mentor, Professor Patricia Wittkopp.
“A cell relies on the information encoded in its DNA to function,” explained Lusk. “This information is broadly divided into two classes: some information specifies how to construct proteins, the basic building blocks of the cell, and other, 'regulatory' information specifies where, when, and in what quantity to construct these proteins. While we know how proteins are encoded, the regulatory code is much more complex, and we are only beginning to understand it. Despite this limited understanding, it appears clear that changes to regulatory DNA sequences underlie a great deal of the diversity within and between species. Towards a better understanding of these sequences, here we are trying to uncover how variation in the DNA between species leads to differences in how these species regulate the construction of their proteins.
“In this research, we will work to fill a critical gap in our knowledge of the regulatory code. We know that a given protein's production is regulated through the binding of other specialized proteins to the DNA, but current methods to measure this binding have several limitations that make it difficult to link sequence changes to these binding changes. To address these limitations, we plan to explore two recently developed complementary methods that capture binding much more comprehensively. We will also use hybrids between different Drosophila species to assess how the regulatory information in DNA sequences can be decoded differently by different sets of binding proteins. We will integrate these data with a rich set of expression differences between these species that has already been collected, allowing us to address several fundamental questions about the nature of the regulatory code, shedding light upon the processes by which organisms evolve.
“The future implications of this line of work are pretty intuitive – errors in regulatory DNA sequences are known to contribute to a wide range of genetic diseases and cancers, but our relative lack of understanding of how these sequences work (compared to, say, protein-coding sequences, which are very well understood) makes it very difficult to infer what's going on in these pathologies (or whether these pathologies are likely to crop up later) from the changes that we can see in an individual's DNA sequence. By getting a better understanding of the impact of sequence variants in regulatory DNA, we become better able to interpret human DNA sequences in useful ways.”
Dr. Ruth L. Kirschstein, for whom the awards were named, died October 6, 2009. Aside from Kirschstein’s scientific accomplishments in polio vaccine development, and becoming the first woman director of an NIH Institute, she was a champion of research training and a strong advocate for the inclusion of underrepresented individuals in the scientific workforce.