Project Grant R16GM146606
- The Research Foundation for the State University of New York (SUNY) received a $400,000 Project Grant from the National Science Foundation (NSF) Division of Molecular and Cellular Biosciences under CFDA 47.074 - Biological Sciences. The project aims to improve understanding of the DNA mismatch repair (MMR) pathway and how changes in the behavior of mismatch repair proteins can lead to genome instability, particularly in the presence of specific DNA sequences like repetitive elements. Key project...
- This Project Grant award from the National Science Foundation's Biological Sciences program (CFDA 47.074) provides $495,594.00 to the University of California, Santa Barbara to conduct research on the mechanisms underlying DNA double-strand break repair through homologous recombination. The objectives of this 5-year project are to 1) define the steps in recombination altered by DNA interstrand crosslinks, 2) explore how the DNA repair regulatory kinase ATR is activated during double-strand break...
- This $2,285,694 project grant from the National Science Foundation's Biological Sciences program (CFDA 47.074) supports research at Tufts University to study the relationship between DNA replication and tandem repeat instability. The grantee will combine genetic assays and single-cell live microscopy analysis in a model system to understand how repeat length changes during replication. This dual approach will examine how a repeat's length, propensity to form DNA structures, and orientation...
- This Project Grant award, provided by the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), supports fundamental scientific research to study the mechanisms of how homologous recombination maintains genomic stability and induces genome rearrangements. The $305,927 award, effective September 1, 2025, will enable researchers at the University of California, Davis to advance their work on understanding the processing of...
- This $900,000 federal Project Grant awarded by the National Science Foundation (NSF) Biological Sciences program (CFDA 47.074) supports a collaborative research project led by North Carolina State University to unravel the mechanisms behind the workings of the DNA mismatch repair systems. The research aims to elucidate the role of atypical nucleic acid structures, such as three-way junctions and R-loops, in driving the expansion of simple sequence repeats (SSRs) within the genome, which is a...
- This Project Grant award from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training program (CFDA 93.859) provides $390,000.00 to The Regents of the University of Colorado (University of Colorado-Denver) to conduct research on the molecular mechanisms of DNA replication during mitosis. The research aims to uncover how cells complete replication of the entire genome before cell division, even when replication is not fully finished in the S phase of...
- This Project Grant award of $254,919.00 from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) supports research at the University of California, San Diego (UCSD) to investigate the regulatory mechanisms that ensure accurate transmission of the genome during cell division. Specifically, the research aims to study how post-translational modification enzymes regulate the assembly and function of DNA replication...
- This federal Project Grant award of $390,000.00 from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), supports research to elucidate the mechanisms underlying DNA double-strand break repair at Thomas Jefferson University, doing business as Sidney Kimmel Medical College. The research aims to determine the regulatory mechanisms of the multi-protein and multi-step process required to coordinate the repair of DNA...
- This $516,608 Project Grant awarded by the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) supports research to understand the mechanisms and regulation of DNA recombination in budding and fission yeast. The key research focus areas are: 1) studying DNA end resection, the critical first step in homologous recombination, within heterochromatin regions, 2) investigating how lagging strand synthesis proceeds during...
- This Project Grant award from the National Science Foundation's (NSF) Biological Sciences program will fund research to investigate the evolution of DNA replication timing in great apes, including humans and chimpanzees. The $406,525 award to Health Research, Inc. will measure DNA replication progression across chromosomes, identify differences, and link variations in replication timing to factors like mutation rates, gene expression, and the evolution of new traits. The research aims to...
CAUSES AND CONSEQUENCES OF BLM-DEPENDENT DNA REPLICATION CHALLENGES - MAINTAINING THE INTEGRITY OF GENOMIC DNA IS CRUCIAL TO CELLULAR FUNCTION AND SURVIVAL. PROTEINS SUCH AS BLOOM (BLM) DNA HELICASE FUNCTION TO PROTECT THE GENOME FROM THE DELETERIOUS EFFECTS OF BOTH EXOGENOUS AND ENDOGENOUS SOURCES OF DNA DAMAGE. LOSS OF BLM ACTIVITY IN HUMANS LEADS TO THE RARE AUTOSOMAL RECESSIVE DISORDER BLOOM SYNDROME, WHICH IS CHARACTERIZED BY DEVELOPMENTAL ABNORMALITIES, PREMATURE AGING, AND CANCER SUSCEPTIBILITY. THE GOAL OF THIS PROPOSED RESEARCH IS TO INVESTIGATE THE ROLE THAT BLM PLAYS IN PREVENTING DNA DAMAGE ASSOCIATED WITH REPETITIVE DNA SEQUENCES. DUE TO THE FUNCTIONAL CONSERVATION BETWEEN HUMAN BLM AND DROSOPHILA MELANOGASTER BLM PROTEINS, WE PROPOSE TO USE DROSOPHILA AS A MODEL FOR STUDYING THE BLM-DEPENDENT REPLICATION CHALLENGES POSED BY REPETITIVE DNA SEQUENCES. THE CELLULAR CONSEQUENCES OF REPEAT-DEPENDENT REPLICATION CHALLENGES TO BLM REMAIN UNKNOWN, BUT THE DROSOPHILA EMBRYO PROVIDES US WITH A USEFUL MODEL FOR STUDYING THESE ASPECTS OF BLM FUNCTION. OUR PREVIOUS DATA SUGGEST THAT BLM FACILITATES REPLICATION OF REPETITIVE DNA SEQUENCES, PARTICULARLY THE HIGHLY REPETITIVE Y CHROMOSOME, DURING EARLY EMBRYO DEVELOPMENT. WE PROPOSE TO IDENTIFY THE REPETITIVE SEQUENCES ON THE Y CHROMOSOME THAT POSE BLM-DEPENDENT REPLICATION CHALLENGES AND TO INVESTIGATE LONG-TERM EFFECTS OF BLM-DEFICIENCY DURING EARLY DEVELOPMENT. WE WILL ADDRESS THESE QUESTIONS IN AIM 1 BY EXPLOITING NATURAL VARIATION IN Y-LINKED REPETITIVE DNA SEQUENCES IN DROSOPHILA TO DEFINE SPECIFIC BLM-DEPENDENT SEQUENCE MOTIFS ON Y CHROMOSOMES. TO ACCOMPLISH THIS, WE WILL SCREEN FOR LINES DISPLAYING Y-LINKED, BLM-DEPENDENT VARIATION AND THEN ANALYZE WHOLE GENOME SEQUENCES OF THESE LINES FOR DIFFERENCES IN Y CHROMOSOME REPETITIVE DNA CONTENT. LONG-TERM BIOLOGICAL EFFECTS OF BLM-DEFICIENCY DURING EMBRYOGENESIS WILL BE INVESTIGATED IN AIM 2 BY COMPARING BLM HETEROZYGOUS FLIES THAT DEVELOPED WITH OR WITHOUT MATERNAL BLM FOR A VARIETY OF PHENOTYPES THAT MIGHT BE AFFECTED BY SUB-LETHAL AMOUNTS OF DNA DAMAGE. THOSE PHENOTYPES WILL INCLUDE LIFESPAN, FERTILITY, BODY COMPOSITION, AND LOCOMOTOR ACTIVITY. LASTLY, IN ALIGNMENT WITH THE GOALS OF THE SURE PROGRAM, AIM 3 OF THIS GRANT WILL PROVIDE HIGH-IMPACT INTENSIVE UNDERGRADUATE RESEARCH TRAINING OF UNDERGRADUATE STUDENTS WHO ARE UNDERREPRESENTED IN BIOMEDICAL RESEARCH. THIS PROPOSAL WILL PROVIDE STUDENTS WITH DIRECT PARTICIPATION IN THE EXECUTION, ANALYSIS, AND REPORTING OF THIS RESEARCH AND WILL SUPPORT THE GROWING REPUTATION OF LC STATE AS A VIBRANT INSTITUTION FOR FUTURE BIOMEDICAL SCIENTISTS AND HEALTHCARE PROFESSIONALS THAT COME FROM DIVERSE BACKGROUNDS.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $168.8k | 8/19/25 | ||
| Not listed | $168.8k | 8/19/24 | ||
| Not listed | $168.8k | 7/27/23 | ||
| Not listed | $0 | 11/11/22 | ||
| Not listed | $0 | 11/11/22 |