Funding is sought for a five year mentored training period at Brown University for Dr. Nicola Neretti to transition from physics to independent investigator in computational biology. The candidate has a Physics PhD from Brown University, and has been working in the field of signal processing and machine learning. During the past year he has been part of a collaborative project with Dr. John Sedivy (Department of Molecular and Cell Biology and Biochemistry) which resulted in a published paper about the analysis of gene expression array data to target c-Myc-activated genes with a correlation-based method. He has established other productive collaborations with members of the Center for Computational Molecular Biology (CCMB) at Brown University. The principal mentor will be Dr. Marc Tatar (Department of Ecology and Evolutionary Biology). The secondary mentors will be Dr. Charles Lawrence (Dep. Applied Mathematics) and Dr. John Sedivy. The work plan for the five years is to split the training/research effort evenly between computation and biology. For the training requirements the candidate plans to attend courses and workshops in genetics, biochemistry, molecular biology, bioinformatics, and related fields. Dr. Neretti also plans to complete lab rotations in the laboratory of Dr. Marc Tatar and Dr. John Sedivy, to acquire first hand experience in generating the biological data he will later analyze. The main focus of the research effort will be to use microarray data in time course experiments with a high temporal resolution to elucidate the complex interactions among genes and develop novel analytic techniques in functional genomic. In particular, the candidate proposes to integrate the results of gene clustering/graph analysis (e.g. correlation and tagged correlation based clustering) obtained from the time course data with the information available in genetic/pathway databases relevant to the process of senescence. This will allow the evaluation of given hypotheses about functional relationships among genes and the identification of novel dependencies, which can then be directly tested via experiments in model systems of aging. By using this approach the candidate proposes to address key questions in aging research such as what transcriptional changes are under the control of a nutrient sensing system, the temporal and hierarchical relationship of these changes, the magnitude of change that is biologically relevant, and whether genes within a functional metabolic network are co-regulated at the transcriptional level.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25AG028753-05
Application #
8113231
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Velazquez, Jose M
Project Start
2007-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$119,416
Indirect Cost
Name
Brown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
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Wood, Jason G; Jones, Brian C; Jiang, Nan et al. (2016) Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc Natl Acad Sci U S A 113:11277-11282
Criscione, Steven W; Theodosakis, Nicholas; Micevic, Goran et al. (2016) Genome-wide characterization of human L1 antisense promoter-driven transcripts. BMC Genomics 17:463
Criscione, Steven W; De Cecco, Marco; Siranosian, Benjamin et al. (2016) Reorganization of chromosome architecture in replicative cellular senescence. Sci Adv 2:e1500882
Criscione, Steven W; Zhang, Yue; Thompson, William et al. (2014) Transcriptional landscape of repetitive elements in normal and cancer human cells. BMC Genomics 15:583
Lamming, Dudley W; Demirkan, Gokhan; Boylan, Joan M et al. (2014) Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2). FASEB J 28:300-15
Ding, Feifei; Gil, M Pilar; Franklin, Michael et al. (2014) Transcriptional response to dietary restriction in Drosophila melanogaster. J Insect Physiol 69:101-6
Whitaker, Rachel; Gil, M Pilar; Ding, Feifei et al. (2014) Dietary switch reveals fast coordinated gene expression changes in Drosophila melanogaster. Aging (Albany NY) 6:355-68
De Cecco, Marco; Criscione, Steven W; Peckham, Edward J et al. (2013) Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell 12:247-56
Antosh, Michael; Fox, David; Cooper, Leon N et al. (2013) CORaL: comparison of ranked lists for analysis of gene expression data. J Comput Biol 20:433-43

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