Difference: PeterLipke (3 vs. 4)

Grant Number: 5S06GM076168-04 Project Title: MBRS Support of Research Excellence at Brooklyn College PI Information: Name Email Title LIPKE, PETER N. plipke@brooklyn.cuny.edu PROFESSOR

Abstract: DESCRIPTION (provided by applicant): Brooklyn College of the City University of New York is a large, diverse urban campus with just under 50% minority students. The college has an enrollment of approximately 11,000 undergraduates and approximately 4,500 Master's students. We also participate in doctoral training with highly regarded on-campus doctoral programs in the sciences as part of the Graduate Center of CUNY. The college values teaching and has a strong record of sending a diverse group of students on for research doctorates. Our faculty members mentor several hundred students a year, including many underrepresented minority students, in laboratory-based research. The College has designated 11 biomedical research faculty to take part in this first SCORE project. The project will allow SCORE participants to increase their research capabilities and productivity and to contribute fully to strengthening of the institution's research culture and reputation. The overall goals of the project are: (1) To increase SCORE faculty research productivity by adding to the number of postdoctoral fellows, graduate students and undergraduate students working in SCORE-supported research labs; by increasing the research infrastructure by adding key laboratory equipment, a bioinformatics/modeling facility and replacing an old and unreliable cage washer; and fostering increased collaboration of investigators with both Brooklyn College faculty and with external scientists. (2) To increase research competitiveness of SCORE faculty by increasing the number of referred publications submitted and published, of presentations given at national conferences, and of external grant submissions and awards; by adding new SCORE investigators as supplemental projects in the first year of the project; by bringing a number of prominent scientists to campus to present their work and discuss research issues with SCORE faculty; and by providing faculty development workshops on skills that successful research scientists need to master to be productive and successful as they balance research, teaching, mentoring, publishing, and service to the college community. (3) To increase the number of minority faculty at the College involved in biomedical research by developing a detailed and proactive plan for diversity science hiring efforts in conjunction with our administration, our departmental hiring committees, and an external advisory committee. The College President has agreed to set a target of hiring one minority science faculty member per year for the four years of the SCORE project.

Public Health Relevance: This Public Health Relevance is not available.

Thesaurus Terms: university

Institution: BROOKLYN COLLEGE 2900 BEDFORD AVE NEW YORK, NY 11210 Fiscal Year: 2009 Department: BIOLOGY Project Start: 02-MAR-2006 Project End: 28-FEB-2010 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: MPRC

Abstract: DESCRIPTION (provided by applicant): Cell surface adhesins mediate the first interactions of fungi with mammalian hosts, so adhesin-mediated binding is a prelude to differentiation, colonization, biofilm formation and pathogenic invasion. These events in turn lead to complications of morbidity and mortality, especially common in immunocompromised and chronic disease patients. The C. albicans Als adhesins are implicated in pathogenesis and biofilm formation. They bind to mammalian tissues, cause fungal cell aggregation, and also co-aggregate with other microbial pathogens to mediate polymicrobial infections. Als adhesins are also important in formation of persistent and drug-resistant biofilms in tissues and on indwelling devices. Our long-term goal is to understand the roles for cell adhesion proteins in fungal life cycles and pathogenesis. The central hypothesis of this proposal is that amyloid-forming sequences are a feature of biofilm-forming adhesins, and these sequences potentiate adhesion, fungal aggregation and host invasion. This hypothesis is based on our findings that Als5p causes adherence with amyloid-like features, that the purified Als5p can form authentic amyloids, and that bioinformatic analyses reveal amyloid-forming sequences in many biofilm-associated microbial adhesins. Three specific aims will test the amyloid/ biofilm hypothesis: (1) To determine the role of specific sequences in amyloid formation and microbial adherence, we will test the working hypothesis that the amyloid-forming sequences are essential for Als-mediated cellular aggregation. (2) We will test the hypothesis that these amyloid-forming sequences in Als proteins are essential for Als-initiated biofilm formation. (3) In Als proteins, glycosylated tandem repeats follow the amyloid-forming sequences, and these repeats greatly increase adhesion activity. We will therefore test the hypothesis that the peptide sequences and glycosylation patterns in the Als repeats modulate amyloid formation to promote cellular aggregation and biofilm formation. The proposed work is innovative in its conjunction of two important concepts: amyloid-like protein interactions and adherence of pathogens leading to biofilm formation. We are also the first group to work on structure and function of Thr-rich repeat sequences in pathogenic and other fungal adhesins. Completion of these aims will lead to better defined models for the initial events in biofilm formation, and will discover whether amyloid-forming sequences are essential for biofilm adherence in fungi. If the hypothesis is supported, the results will establish connections between searches for anti-biofilm and anti-amyloid therapeutic agents.

Public Health Relevance: This Public Health Relevance is not available.

Thesaurus Terms:

There are no thesaurus terms on file for this project.

Institution: BROOKLYN COLLEGE 2900 BEDFORD AVE NEW YORK, NY 11210 Fiscal Year: 2008 Department: BIOLOGY Project Start: 20-JUN-2008 Project End: 30-APR-2012 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZGM1