Visiting Assistant Professor
|Title||Visiting Assistant Professor|
|Work Location||204A Druckenmiller Hall|
B.A., Biophysical Chemistry, Dartmouth College, 1999
Ph.D., Molecular and Cell Biology, University of California, Berkeley, 2007
My research is focused on microbial sugar biochemistry. There are two main research projects in my lab:
The role of trehalose in mycobacterial cell wall construction.
Trehalose is a common disaccharide found in microbes, plants and some invertebrates. It is commonly used as a stress protectant, shielding an organism from salt or thermal stress. In extreme circumstances, it can actually replace water molecules and protect an organism from dehydration. Dry yeast packets that you can buy at the grocery store are a good example of this power of trehalose.
Mycobacteria, including the pathogen Mycobacterium tuberculosis, appear to have an added function for trehalose beyond its use as a stress protectant. My studies in a nonpathogenic relative of M. tuberculosis, M. smegmatis, have indicated that the bacteria cannot survive without a source of trehalose. This is in contrast to E. coli or baker’s yeast, where the microbes can survive without a functional trehalose biosynthetic pathway unless they are stressed by extreme temperatures.
M. smegmatis, however, requires trehalose whether or not the bacteria are placed under stressful conditions. Additionally, M. smegmatis enzymatically modifies the sugar, attaching a large lipid group. This modification drastically alters the biochemical properties of the compound. While it is no longer suited to protect mycobacteria from stress, it appears this trehalose-containing glycolipid is needed for construction of the mycobacterial cell wall. Mycobacteria have notoriously thick, hydrophobic cell walls, and it appears this trehalose-containing glycolipid is a necessary component of their construction. Thus, they require trehalose under all circumstances.
Several important questions remained to be answered in this field. Why is trehalose, and no other sugar, suitable for this component of the cell wall? What is the enzyme responsible for adding the lipid onto trehalose? Since human beings do not make trehalose themselves, the enzyme responsible for modifying trehalose could be an important drug target.
Concerns about long-term energy supply and national security have prompted a recent interest in bioethanol as a source of fuel. While a great deal of research has been concentrated on bioethanol derived from corn, there are other alternatives that avoid some of the drawbacks in obtaining fuel from a source of food.
Cellulosic bioethanol is one of these alternatives. Cellulose is a polymer of the sugar glucose, and is found in all plants. While the yeast that brew ethanol cannot metabolize cellulose on its own, they could use plants as sugar source if the cellulose was broken down first. This process would have the distinct advantage of using a cheap, renewable source of sugar, instead of food.
Animals such as termites and cows can digest cellulose with the aid of symbiotic bacteria in their stomachs. These bacteria possess enzymes that can break down cellulose into its glucose monomers. While some of these enzymes have been isolated, there have been significant hurdles in producing them at high, cost-effective levels with sufficient activity. Research in my lab with explore alternative enzyme sources and protein production methods to achieve this goal.