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Replicative Life Span In Candida Glabrata Case Study

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The goal of this proposed study is to test the hypothesis that replicative life span (RLS) in Candida glabrata enhances azole resistance through regulation of efflux pumps that subsequently leads to drug resistance during infection. Aim 1 is to test whether aging-mediated azole resistance is the result of enhanced transcription for major drug pumps or transport facilitors. Aim 2 is to determine whether the enhanced antiazole activity of the older cells contribute to "clinical" drug resistance. Establishing a correlation between RLS and pathogenicity is a novel concept that the PI has successfully established for the fungal pathogen, Cryptococcus neoformans. In addition, the PI has powerful tools such as the HYAA chip and is poised to …show more content…

albicans. 2. Investigator(s) Strengths • Dr. Fries has considerable training in infectious diseases, pathology, yeast genetics. She is a well-established senior investigator with an extensive publication record. • The PI has previous working experience with RLS in several fungal pathogens including Candida glabrata and has excellent collaborators . Weaknesses • None 3. Innovation Strengths • The HYAA chip assay is a highly innovative technique to assess RLS and morphotype in C. neoformans. • RLS is being examined by the PI in C. neoformans but not in C. glabrata. Study findings that older cells have elevated efflux pumps and are more resistant to antifungals may help to devise new methods of antifungal therapy. Weaknesses • Both HYAA chip assay and RLS vs. drug resistance were previously described by the PI in other organisms. 4. Approach Strengths • Both research aims are well organized and progressive. Each aim contains multiple approaches that help to ensure the likelihood of success. • Preliminary results, though limited, demonstrate that the investigator is fully capable of assessing the role of RLS in drug resistance. • Again, the team has the HYAA-CHIP technology Weaknesses • RLS in C. glabrata may need to

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