Wenxiu MaAssociate ProfessorStatistics Dept wenxiu@ucr.edu(951) 827-6005
CAREER: Computational and statistical methods for allele-specific chromatin structure analysis
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AWARD NUMBER
009595-002
FUND NUMBER
33410
STATUS
Active
AWARD TYPE
3-Grant
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AWARD EXECUTION DATE
3/12/2018
BEGIN DATE
4/1/2018
END DATE
3/31/2023
AWARD AMOUNT
$139,514
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Sponsor Information
SPONSOR AWARD NUMBER
SPONSOR
SPONSOR TYPE
FUNCTION
Organized Research
PROGRAM NAME
Proposal Information
PROPOSAL NUMBER
18010047
PROPOSAL TYPE
New
ACTIVITY TYPE
Basic Research
PI Information
PI
Ma, Wenxiu
PI TITLE
Other
PI DEPTARTMENT
Statistics
PI COLLEGE/SCHOOL
College of Nat & Agr Sciences
CO PIs
Project Information
ABSTRACT
Three-dimensional (3D) genome organization plays an important role in gene regulation. One level of this organization consists of DNA wrapped around histone proteins, and is called the chromatin. High-throughput chromatin conformation capture methods (one example is called the Hi-C assay) have been developed, and yield an immense amount of information about 3D genome organization. However, most current analysis tools cannot distinguish the Hi-C, or equivalent, information that comes from the paired (homologous) maternal and paternal chromosomes in diploid organisms (like humans and other mammals). This means it is not possible to tell if there are different effects arising from the maternal and paternal copies of genes (the alleles). This project will address this problem and allow the development of fine-scale, allele-specific chromatin structures and therefore shed light on the role(s) of chromatin interactions in allelic gene regulation as well as larger principles of genome organization. This research will result in novel computational and statistical methods that combine the analysis of allele-specific chromatin structure with gene expression regulation; the products will include open-source software tools for 3D genome modeling, comparison, visualization, and exploration. These software tools will be made publicly accessible to scientists worldwide. The integrated research and educational activities include curriculum development for both undergraduate and graduate courses in subjects including data science, and statistical and computational genomics. Activities will allow undergraduate students to participate in the research project, as well as training graduate student researchers to acquire interdisciplinary expertise. The project will reach out particularly to middle school students with the goal of engaging young women and underrepresented minority groups in STEM disciplines.
The goal of this project is to (i) establish a new computational and statistical framework for modeling the 3D chromatin structures in an allele-specific manner; (ii) identify structural differences between homologous chromosome pairs; (iii) investigate the impact of chromatin organization on allelic gene regulation; and (iv) understand the interplay between genome architecture and gene function. The project will integrate fine-scale allele-specific chromatin structures with the currently overwhelming amount of one-dimensional functional genomics data to discover new allele-specific regulatory elements and features. The project will elucidate gene regulation principles at an unprecedented resolution, and enhance our understanding of the interplay between genome architecture and gene expression. These findings will have fundamental significance in molecular cell biology, personal genomics, and medicine. Updates and additional information about this project will be made available at http://faculty.ucr.edu/~wenxiu/nsf-1751317.html.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.(Abstract from NSF)
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