Our laboratory is interested in the development and application of strategies and technologies that enable the high-throughput/large-scale exploration of biological function. These efforts typically take advantage of automation and robotics to achieve the efficiencies and speed required to realize the desired rates of data generation and discovery. This cutting-edge infrastructure has been applied to a number of important biomedical areas to achieve new understanding and new therapeutic opportunities.
Our work on the large-scale annotation of enzyme function is helping to define the metabolic repertoire that exists in Nature and is providing new insights into the contributions of the gut microbiome to human health, the realization of new chemical processes for industry, and expanding our understanding of critical environmental issues, including global nutrient cycles and the evolution of complex microbial communities. Our high-resolution structural and functional analysis of the mammalian immune system has resulted in unprecedented understanding of the molecular mechanisms that control immunity and are guiding the development of novel strategies and reagents (e.g., biologics) for the treatment of infectious diseases, autoimmune diseases and cancers.
Humans and other mammals possess an antiviral gene that prevents a remarkable range of viruses from multiplying. Up until recently, we haven’t known this gene’s secret to success.
Scientists do know that this gene codes for an enzyme called viperin.
Now, we’ve discovered how viperin works. Our findings offer an exciting approach for developing new drugs that can attack many disease-causing viruses – but without toxic side effects.
Our research shows that viperin triggers a reaction, within our own cells, that produces a compound called ddhCTP. Remarkably, this compound resembles a number of man-made anti-viral drugs. And based on these similarities, we predicted that this compound would sabotage the process by which viruses copy their own genomes and replicate within cells.
To prove this, we turned to our collaborators at Pennsylvania State University, and, as we had predicted, we found the compound was highly effective in stopping the replication of Zika virus—a mosquito-borne virus that causes an infection for which there is currently no treatment.
Based on additional studies, we believe this compound also may be able to inhibit other viruses, including West Nile, dengue, yellow fever, and hepatitis C virus.
In effect, nature has given us a template for creating a powerful and safe antiviral compound. It’s already in our bodies and it does not interfere with replication of ownour healthy cells – it only affects viruses. Right now, many manmade antiviral drugs are quite toxic and hinder the normal workings of our cells.
We hope we can generate variants of this compound and test them against a broad array of viruses. New drugs based on this naturally-occurring molecule—encoded by the human genome – could have fewer side effects while remaining effective against dangerous viruses that threaten so many people around the world.