Faculty & Staff
Reeta Prusty Rao
Assistant Professor
Faculty Listing
Office: Life Sciences and Bioengineering Center, 4013
Phone: +1-508-831-6120
Fax: +1-508-831-5936
rpr@wpi.edu
Related Information
Educational Background
- B.S., Birla Institute of Technology and Science - India, 1991
- M.S., Drexel University, 1992
- M.S., Drexel University, 1994
- Ph. D., Penn State University, 1999
- Postdoct, MIT/Whitehead Institute, 2005
Research & Teaching Interests
Plant-pathogen interaction; molecular genetics; fungal pathogenesis; quorum sensing
Research
I have had extensive training in Molecular Biology and Genetics and every project in my lab involves one of these aspects of Biology. My model system, S. cerevisiae, is a well-known, safe, facile, and genetically tractable organism, making it an ideal system for using genetics to uncover developmental pathways. Because of the ease of working with S. cerevisiae, the system was the prototype of choice for initiating large-scale projects such as constructing a systematic whole genome knock out collection and performing expression micro-array and proteomic studies. The well-annotated S. cerevisiae database allows easy access to an extensive collection of information and makes it a very attractive organism for undergraduate research. S. cerevisiae has more than withstood the test of time, but has fully demonstrated itself to be a powerful model system that has significantly contributed to science, from understanding the fundamentals of the cell cycle (Nobel Prize in Medicine, 2001) to signaling mechanisms in cancer. I exploit the versatility of this model organism by using a variety of biochemical, genetic, genomic, and behavioral readouts in my studies.
I have developed a system to study intercellular signaling and have discovered that fungi perceive environmental cues and respond to them by switching from a benign yeast form to an infective filamentous form. My objective is to parse out the genetic mechanism whereby a small molecule (namely IAA) regulates pathogenesis. In addition, I will identify the IAA biosynthetic pathway in yeast, which is a prerequisite for IAA to be a quorum-sensing molecule.
Plant Pathogen Interaction
IAA is the major Auxin (growth hormone) in plants and, since Charles Darwin's discovery over 70 years ago, has been implicated in virtually every aspect of plant growth and development. However, the mechanism of IAA perception and signaling still remain elusive. IAA is thought to be synthesized de novo at a wound site on a plant and, taken together with my findings that fungi recognize IAA as a cue to initiate a pathogenic response, suggests that IAA is important in the study of plant-pathogen interaction. I am developing an assay using the model plant Arabidopsis thaliana and yeast to further study plant-pathogen interactions. This will allow us to use a model plant (Arabidopsis) and a nonpathogenic organism (yeast) to study this a very complex phenomenon.
Furthermore, through a genomic mutant hunt, I have identified Grr1 as a component of ubiquitin-ligase complex that is required for the proteolysis of cyclins. This gene could be the missing link between the IAA-mediated growth arrest and IAA-mediated filamentation. My finding is especially pertinent because two independent groups have recently shown that a Grr1 homolog in plants, Tir1, is the IAA receptor in Arabidopsis. It binds IAA and regulates its downstream effects by modulating gene expression.
Molecular Genetics
S. cerevisiae is one of the best organisms for conducting controlled, unbiased large-scale studies. The data from such studies are also available to the scientific community. Using a variety of whole genome studies we have identified and characterized genes involved in regulating filamentation and fungal pathogenesis. For my future research, we will characterize a class of mutants that regulate endocytosis of IAA transporters. We will further characterize the endocytic mutants for IAA mediated filamentation and their ability to import IAA. I predict that decreased endocytosis will lead to the accumulation of IAA transporters at the cell surface, which would cause increased pathogenesis in response to IAA and faster kinetics of IAA import.
Fungal Pathogenesis
Discovery of filamentation in yeast uncovered a mechanism by which pathogenic fungi switch from a benign to infectious form and invade the host tissues. Complicated life cycles render pathogenic fungi recalcitrant to genetic manipulations and, as a result, difficult to manipulate in the laboratory. S. cerevisiae serves as the perfect model to understand fungal pathogens because it shares many of their characteristics and possesses evolutionarily conserved genes. Whole genome profiling of pathogenic fungi can identify key targets that do not occur in humans, providing an opportunity to discover targets for novel antifungal agents. Since the IAA effects observed in yeast are evolutionarily conserved, I will test whether my studies can be extrapolated to pathogens such as C. albicans.
Small Molecule Signaling
Secondary metabolites, like IAA, can be involved in both intra- and interspecies communication mechanisms. The ability to communicate with one another allows microbes to coordinate gene expression, thereby synchronously altering their behavior. Several organisms, including humans, produce IAA as a catabolic product of indoles, such as tryptophan and serotonin. My previous study demonstrated that IAA serves as an extracellular signal. Subsequently, I have discovered that S. cerevisiae can also synthesize IAA. This observation presents the exciting possibility for IAA to be a quorum-sensing molecule, a form of small molecule signaling where the microbe responds differently to varying concentrations of the small molecule. In this case, low concentrations of IAA stimulate filamentation while higher concentrations arrest growth of yeast. I am interested in identifying the exact genetic mechanism of IAA synthesis. This would be one the few studies to parse out the role of small molecule signaling molecules in fungi and how it relates to pathogenesis.
My research will greatly advance our understanding of how secondary metabolites are exploited as signaling molecules in fungi. In the long run, a basic understanding of how fungal secondary metabolites are used as signals that regulate pathogenesis could lead to design of better antifungal agents, of which few are currently known.