Paul Boutz lands first NIH R01 at Rochester
Tuesday, March 2, 2021
Paul Boutz, PhD
Congratulations to Paul Boutz, who received official word that his first NIH R01 application as a faculty member in the Department of Biochemistry and Biophysics at the URMC was funded. Dr. Boutz’s project is entitled "Genomics-based approaches to understanding mechanistic alterations of spliceosome function in disease states” and earned a 12th percentile ranking, meaning the grant application was rated as better than 88% of all other grant applications. The goal of this project is to model genetic perturbations found in cancer and developmental disorders in order to understand how they alter spliceosome function. Conventional and novel RNA sequencing methods will be used to generate genome-wide maps of splicing and RNA-protein interactions that will enable the training of deep-learning neural networks, with the goal of deciphering the codes that confer gene-specific sensitivity to disease-causing mutations.
Wedekind lab research featured on the cover of JBC “The Year in JBC: 2020" issue
Friday, February 12, 2021
Congratulations to Shashank Chavali, Dr. Sachitanand Mali, Dr. Jermaine Jenkins, Dr. Rudi Fasan, and Dr. Joseph Wedekind for being featured on the cover of JBC “The Year in JBC: 2020" issue. Their recent research article, published in the Journal of Biological Chemistry (JBC) December 4, 2020 issue, titled “Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors” has been selected as the representative ‘RNA’ article for 2020 retrospective collection called “The Year in JBC: 2020.”
The cover art below, shows a collage of fluorescence complementation experiments between the [4Fe-4S]-transferring NFU1 and potential partners (performed by Roland et al.), crystal structure overlays of HIV-1 TAR RNA with lab-evolved TAR-binding proteins (reported by Chavali et al.), nonmelanized yeast cells (explored by Chrissian et al.) and a cryo-EM structure of STEAP1, now thought to function as a ferric reductase in heterotrimer form (reported by Oosterheert and Gros). Artwork created by EJ Marklin.
Read More: Wedekind lab research featured on the cover of JBC “The Year in JBC: 2020" issue
Lynne Maquat Awarded 2021 Wolf Prize in Medicine
Tuesday, February 9, 2021
Lynne E. Maquat, Ph.D., the founding director of the Center for RNA Biology at the University of Rochester, was honored with the 2021 Wolf Prize in Medicine. The acclaimed international award is given to outstanding scientists from around the world for achievements that benefit mankind.
Maquat was selected for “fundamental discoveries in RNA biology that have the potential to better human lives.” She has spent her career deciphering the many roles that RNA plays in sickness and in health, and is well known for her discovery of nonsense-mediated mRNA decay or NMD. One of the major surveillance systems in the body, NMD protects against mistakes in gene expression that lead to disease. Maquat’s lab also revealed that NMD helps our cells adjust to changes in development and in their environment, and more rapidly respond to certain stimuli.
Maquat shares the award with Joan Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry at Yale School of Medicine and Adrian Krainer, Ph.D., St. Giles Foundation Professor and Cancer Center Deputy Director of Research at Cold Spring Harbor Laboratory. Steitz and Krainer were also honored for discoveries in RNA biology.
The Wolf Foundation, which celebrates exceptional achievements in the sciences and the arts, is based in Israel, where Maquat’s quest to unravel the intricacies of NMD began. In 1980 she traveled to Jerusalem to retrieve bone marrow samples from four children suffering from thalassemia major, the most severe form of the inherited blood disorder thalassemia. Maquat wanted to learn why the children’s marrow contained no beta-globin protein, which is necessary for the oxygen-carrying function of red blood cells. Her 1981 breakthrough manuscript, “Unstable beta-globin mRNA in mRNA-deficient beta0 thalassemia,” published in Cell, was the first to reveal the role of NMD in human cells and how it can lead to disease.
“Lynne’s work on nonsense-mediated mRNA decay is the bedrock of an ever-growing body of research on how mRNAs are monitored and regulated,” said Mark B. Taubman, M.D., dean of the University of Rochester School of Medicine and Dentistry. “Her dedication to her science and to the field of RNA biology has opened the door to the development of RNA-based therapeutics for a wide range of disorders that you can’t reach with conventional drugs. We’re thrilled that her contributions are being recognized with this prestigious award.”
RNA secured its place in the public eye in 2020 with the development and approval of multiple mRNA COVID-19 vaccines. Years of research by Maquat, Steitz and Krainer helped set the stage for the rapid development of these vaccines.
The J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry, Maquat is the recipient of several other significant honors, including:
Winners of the Wolf Prize are selected annually by an international jury committee of the Wolf Foundation; prizes are awarded regardless of religion, gender, race, geographical region, or political view. The official announcement of this year’s prize by the President of the State of Israel, Reuven Rivlin, was made on February 9, 2021.
Read More: Lynne Maquat Awarded 2021 Wolf Prize in Medicine
UR Center for RNA Biology RNA Presentation Contest Results
Tuesday, February 2, 2021
Thank you to those who participated in and/or viewed the UR Center for RNA Biology's RNA Presentations on Jan 6th, 13th, and 27th, sponsored by the RNA Society and Lexogen. The judging committee was impressed with the quality of the presentations given on all three dates, making final decisions difficult.
All nine of the graduate student, postdoc, and technician presenters, chosen based on their quality of their abstract, will be receiving a one-year membership to the RNA Society. Of these, four who were chosen based on the quality of their presentation will be awarded $375 each to be used toward the attendance of an RNA-centric meeting, in person or virtually.
The four to be awarded a one-year membership in the RNA Society and $375, in alphabetical order, are:
Kamel Awayda (presented Jan 6th )
Technician, Mitch O'Connell Lab
"Characterization of THUMP Domain-Containing Protein 1, and Putative Modulator of RNA Modification"
Chen Bao (presented Jan 13th)
Biochemistry Grad Student, Dmitri Ermolenko Lab
"mRNA Stem-Loops Can Induce Translational Pause through Two Pathways"
Xavier Rambout, PhD (presented Jan 27th)
Postdoc, Lynne Maquat Lab
"Transcriptional Coactivator PGC-1α Contains a Novel CBP80-Binding Motif that Orchestrates Efficient Target-Gene Expression"
Arica VanderWal (presented Jan 13th)
Biochemistry Grad Student, Mitch O'Connell Lab
"The Role of Csx28 in CRISPR-Cas13b Anti-Bacteriophage Defense"
The remaining to be awarded a one-year membership in the RNA Society, in alphabetical order, are:
Lily Cisco (presented Jan 6th )
Pharm-Phys Grad Student, John Lueck Lab
"Testing Therapeutic Intervention for Myotonic Dystrophy Type 1 in a Novel Mouse Model"
Xueyang He (presented Jan 6th )
Biophysics Grad Student, Paul Boutz Lab
"A Novel Method to Capture and Sequence Intron Lariats"
Shon Koren (presented Jan 6th )
Technician, Gail Johnson Lab
"Tau-Ribosome-tRNA Associations Underlie Common Features of Dys sincening Protein Synthesis in Dementia"
Sean Lindley (presented Jan 13th )
Biology Grad Student, Doug Anderson Lab
"StitchR: Ribozyme-Mediated RNA Trans-Splicing and Expression in Mammalian Cells"
Debanjana Maji (presented Jan 27th )
Biophysics Grad Student, Clara Kielkopf Lab
"Representative Cancer-Relevant U2AF2 Mutations Alter RNA Interactions and Splicing"
Beneath the Surface of Fragile X Syndrome: Study Sheds Light on What’s Happening in Nerve Cells
Monday, January 25, 2021
A new study shows that many abnormalities in fragile X syndrome cells are related to glitches with one of the body’s major quality control systems. Published in Nature Cell Biology, the research provides fresh insight into the molecular mechanisms of the disorder and a pathway to search for potential treatments.
Fragile X syndrome occurs when individuals don’t make the fragile X protein known as FMRP, which is needed for normal brain development. Currently, little is known about how the loss of this crucial protein leads to the intellectual disability and severe learning problems characteristic of the disease.
Rochester researchers found that many irregularities in cells that lack FMRP are due to misregulated nonsense-mediated mRNA decay, or NMD. Discovered by RNA biologist Lynne E. Maquat, Ph.D., NMD is like a molecular guide that helps our cells make smart decisions that (in most cases) improve cellular function and contribute to good health. For example, NMD helps our cells adjust to changes in development and in their environment, and more rapidly respond to certain stimuli.
Through a series of cellular analyses, Maquat’s team discovered that NMD influences a wide range of genes throughout the brain, including genes that govern motor control and cognitive processes related to attention, learning and language. They also found that when FMRP is absent from cells, as it is in people with fragile X syndrome, nonsense-mediated mRNA decay shifts into overdrive.Read More: Beneath the Surface of Fragile X Syndrome: Study Sheds Light on What’s Happening in Nerve Cells
New Research Funding Initiative to Support Young Investigators
Friday, January 15, 2021
Thanks to a partnership between pediatric researchers and the GCH Advancement division, a new funding initiative will seek to provide $25,000 – matched with grant funds – to support individual young investigators who are undertaking pediatric research.
These young investigators would be tenure-track assistant professors or post-doctoral fellows who already have a PhD degree and are on the path to obtain a tenure track position. This type of “seed” funding will be critical for fostering the careers of young researchers at URMC and could potentially pay dividends for institutional growth in the long-term, according Tom Mariani, PhD, professor of Neonatology and director of research for the Department of Pediatrics.
“In addition to funding discovery and innovation which could potentially save millions of lives, the career development of one investigator can be leveraged many times over to merit additional external funding, creation of new labs, and stimulate economic growth in the Rochester community.”
Alan Wood, owner of the Realty company RE/Max Plus and supporter of GCH, and Lynne Maquat, PhD, endowed chair and professor in the Departments of Biochemistry and Biophysics, Oncology, and Pediatrics, developing this funding idea after Wood and his children visited Maquat’s Fragile X Syndrome lab this Fall. Fragile X Syndrome is the most common single-gene cause of autism and intellectual disability, and Wood’s family got a thorough education on the scope of Maquat’s work, which is examining disease-causing mutations in children, and what those mutations do to gene expression via RNA production.
“My children loved getting first-hand experience touring the lab and seeing real-world visualizations of the work Maquat and her team are doing. Wearing lab coats and gloves, they isolated genetic material from bananas, which turn out to have more genetic material than us humans,” said Wood.
Wood will be leading the effort to develop the program and secure funding. Donors who sponsor a young investigator will be able to establish a relationship to learn more about their research as it evolves.
“We have several talented young researchers in the Department of Pediatrics,” said Maquat, “providing early support for their career is a long-term goal. The results won’t be immediate, but over time, this support will build the foundation for discovery that will improve kids’ lives.”Read More: New Research Funding Initiative to Support Young Investigators
Alan Grossfield Featured in Biophysical Society Profile
Monday, January 11, 2021
Biochemistry and Biophysics Professor Alan Grossfield was recently featured in a two-page profile piece in the January 2021 Biophysical Society Bulletin. The article details how Dr. Grossfield developed an interest in science and progress from an undergraduate biology major to ultimately making a career in computational studies of biological systems. The entire article can be found here: https://biophysics.cld.bz/Biophysical-Society-Bulletin-January-2021/4/#zoom=z