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Contact Information

Office:
Life Sciences & Bioengineering Center, 4013
Phone: +1-508-831-6120
Fax: +1-508-831-5936
rpr@wpi.edu

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Reeta Prusty Rao

• Assistant Professor, Biology & Biotechnology
• Affiliated with:
  • Biochemistry

Understanding Fungal Pathogenesis
The research goal is to understand and ultimately manage fungal diseases, specifically C. albicans. My laboratory uses a variety of biochemical, molecular genetic, genomic, and behavioral tools and exploits the versatility of model organisms to explore fungal virulence strategies in a high-throughput fashion.  Contribution of individual genes is validated in the human pathogen Candida albicans.

A vast majority of healthy individuals are affected with a candida infection (such as a diaper rash, thrush, or vaginitis) in their lifetime, with half of them suffering from recurring infections.  Immunocompromised individuals (transplant and AIDS patients, neonates, etc.) are susceptible to a bloodstream infection with high mortality rates. The rate of hospital-acquired candida infections is on the rise, partly because therapeutic avenues of managing fungal infections are limited.

We have developed a whole-animal model to understand the genetic and molecular mechanisms of fungal pathogenesis. Using Caenorhabditis elegans as a model host, we have found that fungi (nonpathogenic S. cerevisae or the human pathogen C. albicans) infect the worm, producing visible disease phenotypes and death. Our study is unique because, first, it uses liquid cultures for the microbes as well as egg preparations for the animal host, making it well-suited for high-throughput whole genome analyses. Secondly, our assay allows us to evaluate genetic contributions of the fungal pathogen as well as the host via mutant libraries and RNA interference (RNAi)-mediated knockdown collection, respectively. These unique tools allow us to systematically scan the entire genomes to identify fungal virulence factors and modulators of host immunity to fully understand the pathogenic process, as well as develop better antifungals.

Drug Discovery
In collaboration with researchers at UMass Medical, we have developed assays and initiated high-throughput drug screens to identify chemical inhibitors of C. albicans.

Small Molecule Signaling
Fungi use chemical signals to assess whether conditions are favorable for infection. The ability to communicate with one another allows microbes to coordinate gene expression, thereby synchronously altering their behavior.  Therefore, disrupting these signals would disrupt the infection process. Secondary metabolites, like Indole acetic acid (IAA), are involved in both intra- and interspecies communication mechanisms. 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, several organisms, including humans, produce IAA as a catabolic product of indoles, such as tryptophan and serotonin. We have demonstrated that fungi perceive, synthesize, and respond to IAA. 

We are using genomic and genetic tools to identify components of the IAA signal transduction mechanism in fungi (S. cerevisiae and C. albicans). For example, we have already identified the IAA transporters. We are investigating candidates for putative IAA receptor that would bind IAA and regulates its downstream effects by modulating gene expression.  This 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.

Plant-fungal Interactions
My previous study demonstrated that fungi use the plant hormone IAA as an extracellular signal to initiate the infection process.  IAA is thought to be synthesized de novo at a wound site on a plant.  This suggests that IAA is important in the study of plant-pathogen interaction. We have developed an assay using the model plant Nicotiana benthamiana to further study plant-fungal interactions.

Furthermore, we have discovered that fungi have multiple pathways for IAA synthesis.  We hope to identify the genes for IAA synthesis in yeast, because some of these pathways have been illusive in plants. Our study would not only facilitate their identification, but also parse out the role of small molecule-signaling molecules in fungi and how it relates to plant pathogenesis.

Other Projects
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. For example, we use the powerful genetic and genomic tools available in S. cerevisiae to understand the mode of action of ill-understood drugs at the molecular level. Such information can be used to increase efficacy or decrease side effects of drugs. Finally, we are genetically modifying yeast to increase bio-butanol production from cellulosic feedstock.

Teaching
One of the most important roles of an academic scientist is to be a mentor to students who are in the process of developing their scientific knowledge and research skills. At WPI, I am excited that I am able to reach out to interested undergraduate students at all stages of their college education, perhaps not biologists but nevertheless inspired and educated. I enjoy teaching them how to be a good experimental scientist and watching them learn the scientific way of thinking.

I also have the opportunity to teach and train graduate students. This is a gratifying aspect of my role as a teacher, because graduate students are more mature and motivated.

Finally, I have to opportunity to educate the general public with my research papers and presentations. I work hard to find ways to explain my research without the scientific jargon so that it is accessible to the popular press, not just the scientific community. 

Therefore, in the classroom, I strive to make my courses modern and engaging. Toward this goal, I use outcomes assessment to ascertain in a scientific way what my students are and are not learning. I will use the results to provide evidence for future curriculum change. In my laboratory, I have built an integrated research program, in which students form a strong laboratory, helping each other learn by supervising less-experienced peers.

Courses

• Introduction to Biology (BB1001)
  Student Demographic: Nonmajors to satisfy Science requirement.
  Goal: To make topics meaningful. 
  Approach: Use an “in the news” approach to teaching.
  
• Microbiology (BB2002)
  Student Demographic: Sophomores and juniors, BB, and BC majors.
  Goal: To meet the needs of students bound to healthcare-related fields. 
  Approach: Use a “case study” approach to teaching.
  
• Advanced Molecular Genetics (BB4010, seniors and graduate students, BB, and BC)
  Student Demographic: Seniors, BB, and BC majors.
  Goal: To meet the needs of students bound to healthcare-related fields. 
  Approach: Use the primary literature only (no textbook) to teach.
• Model Systems (BB570)
  Student Demographic: Graduate students, BB, BC, & BME.
  Goal: Gain a working knowledge of model systems used in research. 
  Approach: Educate students through examples on appropriate use of model organisms (choices, benefits, and pitfalls).