Brenton Graveley is a professor and chair of Genetics and Genome Sciences at UConn Health and is associate director of the UConn Institute for Systems Genomics. He is the Health Net, Inc. Endowed Chair in Genetics and Developmental Biology and the director of the UConn Stem Cell Institute.
Brent has studied RNA biology throughout his entire career. He performed his undergraduate studies at the University of Colorado, Boulder with David Prescott, his graduate studies at the University of Vermont with Greg Gilmartin, and his postdoctoral studies at Harvard University with Tom Maniatis. Brent has led large components of the ENCODE and modENCODE projects, studies the mechanisms of alternative splicing using genomic, genetic, and biochemical approaches, and collaborates extensively to investigate various aspects of RNA biology.
Areas of Expertise
University of Vermont
Microbiology and Molecular Genetics
University of Colorado
Molecular, Cellular, and Developmental Biology
Elected Member, Connecticut Academy of Science and Engineering
The future of genetics: UConn professor building ‘encyclopedia’ of human genes
Hearst Connecticut Media print
A team at UConn is part of an international consortium of scientists taking the next step toward the end of congenital disease. The entirety of the human genetic sequence has been mapped for some time. The Human Genome Project finished its work in 1993, but as Brenton Graveley explained, that was only the beginning. It was like having a dictionary, he said, without knowing how to build a sentence.
New insights into human and mouse genomes published in NIH study
Drug Target Review online
“The data generated in ENCODE 3 dramatically increase our understanding of the human genome,” said Professor Brenton Graveley, chair of the Department of Genetics and Genome Sciences at UCONN Health. “The project has added tremendous resolution and clarity for previous data types, such as DNA-binding proteins and chromatin marks and new data types, such as long-range DNA interactions and protein-RNA interactions.”
A better way to read the genome
Genomicists Brenton Graveley from the UConn Institute of Systems Genomics, postdoctoral fellow Mohan Bolisetty, and graduate student Gopinath Rajadinakaran teamed up with UK-based Oxford Nanopore Technologies to show that the company's MinION nanopore sequencer can sequence genes faster, better, and at a much lower cost than the standard technology. They published their findings on Sept. 30 in Genome Biology.
Histones direct site-specific CRISPR spacer acquisition in model archaeonNature Microbiology
2023 CRISPR–Cas systems provide heritable immunity against viruses and other mobile genetic elements by incorporating fragments of invader DNA into the host CRISPR array as spacers. Integration of new spacers is localized to the 5′ end of the array, and in certain Gram-negative Bacteria this polarized localization is accomplished by the integration host factor. For most other Bacteria and Archaea, the mechanism for 5′ end localization is unknown. Here we show that archaeal histones play a key role in directing integration of CRISPR spacers. In Pyrococcus furiosus, deletion of either histone A or B impairs integration.
Investigation of CRISPR-Independent Phage Resistance Mechanisms Reveals a Role for FtsH in Phage Adsorption to Streptococcus thermophilusJournal of Bacteriology
2023 Prokaryotes are under constant pressure from phage infection and thus have evolved multiple means of defense or evasion. While CRISPR-Cas constitutes a robust immune system and appears to be the predominant means of survival for Streptococcus thermophilus when facing lytic phage infection, other forms of phage resistance coexist in this species. Here, we show that S. thermophilus strains with deleted CRISPR-Cas loci can still give rise to phage-resistant clones following lytic phage challenge. Notably, non-CRISPR phage-resistant survivors had multiple mutations which would truncate or recode a membrane-anchored host protease, FtsH.
RBP Image Database: A resource for the systematic characterization of the subcellular distribution properties of human RNA binding proteinsNucleic Acids Research
2023 RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in specific regions of the cell, including nuclear or cytoplasmic locations, defining the subcellular distribution properties of RBPs is an important step in assessing their potential functions. Here, we present the RBP Image Database, a resource that details the subcellular localization features of 301 RBPs in the human HepG2 and HeLa cell lines, based on the results of systematic immuno-fluorescence studies conducted using a highly validated collection of RBP antibodies and a panel of 12 markers for specific organelles and subcellular structures.
Late-life shift in caloric intake affects fly longevity and metabolismbioRxiv
2023 Caloric restriction (CR) delays the onset of age-related changes and extends lifespan in most species, but how late in life organisms benefit from switching to a low-calorie (L) diet is unexplored. We transferred wild type male flies from a high- (H) to a L-calorie diet (HL) or vice versa (LH) at different times. Late-life HL shift immediately and profoundly reduces fly mortality rate to briefly lower rate than in flies on a constant L diet, and increases lifespan. Conversely, a LH shift increases mortality and hazard rate, which is temporarily higher than in flies aged on a H diet, and leads to shorter lifespan. Transcriptomic changes within 48 hours following diet shift uncover physiological adaptations to available nutrients.
Hyper-stimulation of Pyrococcus furiosus CRISPR DNA uptake by a self-transmissible plasmidExtremophiles
2022 Pyrococcus furiosus is a hyperthermophilic archaeon with three effector CRISPR complexes (types I-A, I-B, and III-B) that each employ crRNAs derived from seven CRISPR arrays. Here, we investigate the CRISPR adaptation response to a newly discovered and self-transmissible plasmid, pT33.3. Transconjugant strains of Pyrococcus furiosus exhibited dramatically elevated levels of new spacer integration at CRISPR loci relative to the strain harboring a commonly employed, laboratory-constructed plasmid. High-throughput sequence analysis demonstrated that the vast majority of the newly acquired spacers were preferentially selected from DNA surrounding a particular region of the pT33.3 plasmid and exhibited a bi-directional pattern of strand bias that is a hallmark of primed adaptation by type I systems.