News

Congratulations, Mentoring-Up Resolution Challenge Winners!

Full-time UR grad students (gender-inclusive) in biomedical, biological, or chemical sciences took charge of their futures by setting and, through mentoring-up, achieving professional and personal goals for Spring 2021. Participants submitted their goals in a January write-up and progress reports on their professional goals in May. The anonymous faculty evaluation committee selected finalists to present on May 20^th. All four presenters were selected to win $1500 ea. in technology-related (hardware, software, and/or peripherals) prizes. Of note, submissions for this contest were received from graduate students of 12 different programs!

Graduate Women in Science has been selected for the 2021 Best of Rochester Award in the University category by the Rochester Award Program.

Each year, the Rochester Award Program identifies companies that we believe have achieved exceptional marketing success in their local community and business category. These are local companies that enhance the positive image of small business through service to their customers and our community. These exceptional companies help make the Rochester area a great place to live, work and play.

Various sources of information were gathered and analyzed to choose the winners in each category. The 2021 Rochester Award Program focuses on quality, not quantity. Winners are determined based on the information gathered both internally by the Rochester Award Program and data provided by third parties.

About Rochester Award Program

The Rochester Award Program is an annual awards program honoring the achievements and accomplishments of local businesses throughout the Rochester area. Recognition is given to those companies that have shown the ability to use their best practices and implemented programs to generate competitive advantages and long-term value.

The Rochester Award Program was established to recognize the best of local businesses in our community. Our organization works exclusively with local business owners, trade groups, professional associations and other business advertising and marketing groups. Our mission is to recognize the small business community's contributions to the U.S. economy.

Lynne Maquat, Ph.D., the founding director of the Center for RNA Biology at the University of Rochester, has been awarded the Warren Alpert Foundation Prize for her pivotal discoveries in the field of RNA biology. She shares the prize with fellow RNA biologist Joan Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry at Yale School of Medicine.

The award is given by the Warren Alpert Foundation in recognition of work that has improved the understanding, prevention, treatment or cure of human disease. The prize is administered by Harvard Medical School, and since its inception in 1987, 12 honorees have gone on to receive Nobel prizes.

George Q. Daley, dean of Harvard Medical School, said of Maquat and Steitz: "The discoveries made by the two award winners are stunning in their elegance and scope." Earlier this year, the pair won the 2021 Wolf Prize in Medicine for their work. They shared the Wolf Prize with a third RNA biologist, Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory.

RNA Makes its Mark

Maquat has studied RNA since she started her own laboratory in 1982. But until the development and approval of multiple mRNA COVID-19 vaccines in 2020, RNA wasn't on the public radar. Decades of research by Maquat and Steitz on how RNAs work and how they are involved in human disease helped set the stage for the rapid development of these vaccines, which are key to bringing the COVID pandemic under control.

Many are familiar with DNA, which contains the genetic instructions that make us who we are. But RNA is equally important in the process of gene expression:

• DNA lives in the nucleus of a cell and makes many types of RNA, including mRNA (messenger RNA).
• mRNA takes genetic instructions from DNA, travels out of the nucleus and delivers them to factories in our cells called ribosomes.
• Ribosomes use the instructions to create proteins.
• Proteins carry out myriad functions throughout the body, including ferrying nutrients around, helping with chemical reactions and protecting us from disease.

Many disorders result from problems with our DNA, but over the past several decades Maquat, Steitz and other scientists revealed that mRNA plays a role in a multitude of diseases, too. Cystic fibrosis, fragile X syndrome, Duchene muscular dystrophy and a long list of other inherited and acquired diseases result from defective mRNAs.

"Scientists used to think that gene regulation was all about DNA, and that RNA didn't influence gene expression, the production of proteins or the development of disease," said Maquat, the J. Lowell Orbison Endowed Chair and Professor of Biochemistry and Biophysics, Oncology and Pediatrics at the University of Rochester School of Medicine and Dentistry. "We now know that a very complicated network exists in our cells to regulate how, when and where our mRNAs are produced. This knowledge has opened the door to using RNA as both a treatment target and a tool to develop new therapies."

Dr. Harold Smith

OyaGen, a start-up biotech company founded by Harold Smith, Ph.D., Professor of Biochemistry and Biophysics, announced on Monday a licensing agreement with Tonix Pharmaceuticals to develop a drug that was found to be an effective agent against the virus that causes COVID-19. The drug, TNX-3500, was found to block SARS-CoV-2 with an efficacy significantly greater than the current front-line anti-viral used in the clinic, remdesivir. Harold Smith, PhD, Chief Executive Officer and founder of OyaGen, remarked that "We're delighted to partner with Tonix as a clinical stage company on the development of TNX-3500 as we believe Tonix to be ideally capable to bring this drug lead to the clinic in rapid fashion and position it for worldwide commercialization." Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, is located in Chatham, NJ. For more information please contact Dr. Smith at Harold.smith@rochester.edu

Congratulations to Biochemistry & Biophysics Professor Russell Hilf, Ph.D., as his paper, Fluorimetric method for determination of oxidized and reduced glutathione in tissues, has been read over 2,000 times and cited over 3500 times!

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.

Congratulations Paul!

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 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:

• Wiley Prize in Biomedical Sciences (2018)
• Vanderbilt Prize in Biomedical Science (2017)
• Canada Gairdner International Award (2015)
• RNA Society's Lifetime Achievement Awards in Service (2010) and in Science (2017)
• Election to the National Academy of Medicine (2017), the National Academies of Sciences (2011) and the American Academy of Arts and Sciences (2006) More about Nonsense-Mediated mRNA Decay

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.

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 6^th )

Technician, Mitch O'Connell Lab

"Characterization of THUMP Domain-Containing Protein 1, and Putative Modulator of RNA Modification"

Chen Bao (presented Jan 13^th)

Biochemistry Grad Student, Dmitri Ermolenko Lab

"mRNA Stem-Loops Can Induce Translational Pause through Two Pathways"

Xavier Rambout, PhD (presented Jan 27^th)

Postdoc, Lynne Maquat Lab

"Transcriptional Coactivator PGC-1α Contains a Novel CBP80-Binding Motif that Orchestrates Efficient Target-Gene Expression"

Arica VanderWal (presented Jan 13^th)

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 6^th )

Pharm-Phys Grad Student, John Lueck Lab

"Testing Therapeutic Intervention for Myotonic Dystrophy Type 1 in a Novel Mouse Model"

Xueyang He (presented Jan 6^th )

Biophysics Grad Student, Paul Boutz Lab

"A Novel Method to Capture and Sequence Intron Lariats"

Shon Koren (presented Jan 6^th )

Technician, Gail Johnson Lab

"Tau-Ribosome-tRNA Associations Underlie Common Features of Dys sincening Protein Synthesis in Dementia"

Sean Lindley (presented Jan 13^th )

Biology Grad Student, Doug Anderson Lab

"StitchR: Ribozyme-Mediated RNA Trans-Splicing and Expression in Mammalian Cells"

Debanjana Maji (presented Jan 27^th )

Biophysics Grad Student, Clara Kielkopf Lab

"Representative Cancer-Relevant U2AF2 Mutations Alter RNA Interactions and Splicing"

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.

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."

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

The Department of Biochemistry and Biophysics recently held its 1st Annual Holiday Decorating Door contest. With only two labs participating in this year's contest, both labs were declared as winners. Congratulations to the Boutz Lab and the O'Connell lab!

O'Connell lab door

Boutz lab door

View Enlarged Thank You Letter

The Department of Biochemistry and Biophysics held its annual toy drive this season to collect toys and items for the Golisano Children's Hospital. Dr. Alan Grossfield delivered a cart full of goodies to the Golisano Children's hospital on Tuesday, December 15th. The gifts are given to the children in the hospital during the holiday season. Any remaining gifts are used to support the needs of the children and playrooms throughout the year.

The US Food and Drug Administration recently approved emergency use authorization for a COVID-19 vaccine developed by Pfizer and the German pharmaceutical company BioNTech.

The vaccine made history not only because it reported a 95 percent efficacy rate at preventing COVID-19 in clinical trials, but because it is the first vaccine ever approved by the FDA for human use that is based on RNA technology.

"The development of RNA vaccines is a great boon to the future of treating infectious diseases," says Lynne Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor in biochemistry and biophysics, oncology, and pediatrics at Rochester and the director of Rochester's Center for RNA Biology.

COVID-19, short for "coronavirus disease 2019," is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in ribonucleic acid (RNA). The viral RNA is sneaky: its features cause the protein synthesis machinery in humans to mistake it for RNA produced by our own DNA.

For that reason, several of the leading COVID-19 vaccines and treatments are based on RNA technology.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. This RNA research provides an important foundation for developing vaccines and other drugs and therapeutics to disrupt the virus and stop infections.

"Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA does—make new virus that can infect more of our cells and also the cells of other human beings," Maquat says.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, "the RNA research world has exploded," Maquat says. "The University of Rochester understood this."

In 2007, Maquat founded The Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The Center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

Congratulations to Dan Steiner for winning a Sayeeda Zain Fall travel award. Dan is planning to attend the SPIE Photonics West meeting, to be held at the Moscone Center, San Francisco, California, March 6-11, 2021, He states "I am excited to represent our department and present my work in San Francisco (virtually or otherwise) . Networking and reaching out to labs and PIs at this conference will help me learn more about the entrepreneurial side of science and how to develop my career after I defend." The Sayeeda Zain Travel Award honors the distinguished career and charitable life of Dr. Sayeeda Zain. The award is given in recognition of research excellence to support expenses associated with attendance at a scientific conference or corporate internship to gain practical experience. Dan Steiner is a Biophysics graduate student studying in Dr. Ben Miller's lab

How do you make an impact when you are the only person in the room that looks like you? We hear the terms diversity and inclusion but forget that the term representation should be a reflection of diversity and inclusion combined. This isn't always the case. Dr. Grayson discusses her views on what it means to increase diversity and representation as an Individual Contributor. Learn more about her journey as the 2nd Black Woman to graduate with a PhD in Mechanical Engineering from her graduate institution. Hear about her current work as both an engineer, a STEM Advocate, and her most recent success as author of 'HOODED: A Black Girl's Guide to the PhD' where she highlights her time and lessons learned during her PhD Program.

 

Nazish Jeffery

Graduate student Nazish Jeffery published an editorial-style column entitled "Scientists Must Communicate More Clearly" which appeared on the Opinion page of the Sunday, October 4th edition of the Democrat and Chronicle. Ms. Jeffery argues that scientist have a civic duty to clearly inform and educate the public and public officials with regard to the results of biomedical research. She states "As scientists, our civic duty becomes twofold. Not only must we better our understanding of the world through research, we also need to use our training and expertise to help inform who govern so they can craft policies that are scientifically sound." Ms. Jeffery will be taking a brief hiatus from her laboratory research in Michael Bulger's lab to remotely participate in an internship with the American Institute of Biological Sciences in Washington DC, where she will focus on science and public policy.

Clara Kielkopf, Ph.D., left, and Laura Calvi, M.D., stand by the University's new cryo-microscope

With the recent acquisition of Nobel Prize-winning technology and two new grants, Wilmot Cancer Institute researchers are streamlining their investigations into a malignant blood disease known as MDS, working toward discovering targeted therapies.

Laura Calvi, M.D., and Clara Kielkopf, Ph.D., are leading collaborative teams that will be using a device at the University of Rochester Medical Center — a cryo-electron microscope — that has ushered in a new era in biochemistry. The microscope allows scientists to see 3D snapshots and more details of living molecules than ever before, down to near-atomic resolution, to understand disease and uncover new ways to design drugs. The developers of the technology were awarded the Nobel Prize in Chemistry 2017.

Calvi and Kielkopf each received Edward P. Evans Foundation awards totaling $1.2 million for this project. Evans grants go to scientists seeking a cure for myelodysplastic syndromes (MDS), which originates in the bone marrow and disrupts healthy blood cell formation. MDS often leads to leukemia.

The Kielkopf lab will use the cryo-electron microscope to obtain 3D views of recurrent MDS mutations as guides for targeting molecular therapies. The modern microscope is the first of its kind in the Rochester region, Kielkopf said, and will be accessible to all UR researchers through the Electron Microscopy Shared Resource Laboratory. She is a professor of Biochemistry and Biophysics in the Center for RNA Biology.

We are thrilled to announce that Professor David Mathews, MD, PhD, was honored at this year's School of Medicine Opening Convocation by being installed as the first Lynne Maquat Distinguished Professor in RNA Biology in the School of Medicine and Dentistry. The professorship was awarded by Dr. Mark Taubman, Dean of the School of Medicine and CEO of the University of Rochester Medical Center. The Convocation was held virtually this year and can be viewed at the link below.

Congratulations to Professor Mathews!

Adrian Vargas, a pre-doctoral student in the laboratory of Dr. Mitch O'Connell successfully defended his Qualifying Exam proposal entitled "Understanding guide-RNA design rules for efficient and specific Cas13 RNA-binding in human cells". Working on the recently described Type VI CRISPR-Cas system Adrian is investigating unique properties of the effector nuclease Cas13. His work has designed new approaches that will shed light on the mechanisms that govern optimal Cas13 RNA-binding, and potentially enhance its usability in human cells. Pursuing such goals not only will help complete our understanding of the gRNA requirements for on-target efficiency but more importantly, it will assist in uncovering what gRNA features contribute to off-target effects that could hinder the use of Cas13 as a specific RNA-targeting tool. The results will develop a more holistic biophysical model of Cas13 binding and cleavage activity. Congratulations Adrian on a job well done! You can read Adrian's thesis abstract below.

Title: Understanding guide-RNA design rules for efficient and specific Cas13 RNA-binding in human cells.

Abstract: Prokaryotic adaptive immune systems utilize Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR Associated (Cas) proteins to target and cleave foreign genetic elements in an RNA-guided manner. The recently described Type VI CRISPR-Cas system contains a single effector ribonuclease, Cas13, that binds and processes a guide-RNA (gRNA), forming an RNA-guided RNA-targeting protein complex. Cas13 has been successfully engineered for potent RNA-knockdown in eukaryotic cells with minimal off-target effects, and other exciting applications described to date include utilizing a nuclease-dead Cas13 (dCas13) as a programmable RNA-binding protein for RNA imaging, RNA-splicing, RNA-detection or RNA-editing applications, among others.

However, the principles of guide-RNA selection for efficient and specific Cas13:gRNA RNA binding remain elusive. Previous work indicates that gRNA choice is important because not all gRNAs yield a robust RNA-targeting, and it is likely that there are different gRNA requirements for RNA-binding compared to RNA-cleavage applications. Furthermore, no predictive models exist for guide-RNA binding efficiency and specificity for Cas13 because no systematic screens have been carried out. Given that no transcriptome-wide measurements of Cas13-binding specificity have been attempted so far, it is unknown what the Cas13 off-target landscape is for human cells. Addressing this knowledge gap and quantitatively understanding the differences between binding and cleavage specificities is integral to the development of specific Cas13 RNA-binding applications.

In this project, I propose a series of approaches that will shed light on the mechanisms that govern optimal Cas13 RNA-binding, and potentially enhance its usability in human cells. Pursuing such goals not only will help complete our understanding of the gRNA requirements for on-target efficiency but more importantly, it will assist us in uncovering what gRNA features contribute to off-target effects that could hinder the use of Cas13 as a specific RNA-targeting tool, particularly for RNA-binding applications. In addition, these findings will be complemented by kinetic studies to dissect the biochemical components underlying Cas13 binding specificity to develop a more holistic biophysical model of Cas13 binding and cleavage activity. Consequently, we will generate a predictive model for Cas13 guide-RNA targeting specificity which will be complied into a comprehensive gRNA design tool tailored to different RNA-targeting applications for any RNA of choice. Finally, using the knowledge we generate and existing structural information, we will attempt to rationally engineer Cas13 and gRNA structure to enhance binding (and cleavage) specificities. Taken together, this work will bolster efforts to develop a range of RNA-targeting tools that can be readily used as research tools to address knowledge gaps in RNA biology, and as potential therapeutics.

The UR Center for RNA Biology offered an exercise during the time when COVID-19 became a sufficient threat to largely shut-down our research enterprise. We're pleased to announce the winners of the UR's Center for RNA Biology Essay Contest on "The role of RNA research in community health". These awards are sponsored by a grant from the RNA Society & Lexogen to the UR Center for RNA Biology, and funds from UR RNA Structure & Function Cluster.

Our Gold prize (~$1,000 value) award goes to Sydney Simpson, an Immunology, Microbiology & Virology graduate student in Steve Dewhurst's lab in the Department of Microbiology & Immunology, for her essay: "Nucleoside Analog Inhibitors: Timeless & Timely Beacons of Hope".

The Silver Prize (~$250 value) award goes to Omar Hedaya, a Biochemistry & Molecular Biology graduate student in Peng Yao's lab in the Department of Medicine/Department of Biochemistry & Biophysics, for his essay: "Know the Fundamentals when Seeking the Future".

Omar Hedaya

Sydney Simpson

Both awardees have become members of the RNA Society and will use their winnings toward technology needs for the upcoming semester.

The RNA Society now features our contest results, including the winning essays, in its latest RNA Salon update: https://www.rnasociety.org/featured-salons, see bullet #3.

We would like to acknowledge Honorable Mentions for the following applicants:

• Sai Shashank Chavali -- Graduate student; Biophysics, Structural & Computational Biology; Wedekind Lab
• Lily Cisco -- Graduate student; Cellular and Molecular Pharmacology & Physiology; Lueck Lab
• Gabrielle Kosoy -- Graduate student; Biophysics, Structural & Computational Biology; Miller Lab
• Ashwin Kumar -- Graduate student; Biophysics, Structural & Computational Biology; Topham Lab
• Li Xie -- Graduate student; Genetics, Development & Stem Cells; Pröschel Lab

We thank all who participated -- and our judges, too!

Prof. Clara Kielkopf has been awarded an EvansMDS research grant to use the new, state-of-the-art cryo-electron microscope at the U of R Medical Center EM facility. The Kielkopf group will use this revolutionary technique to study 3D structures of mutant U2AF1-splicing complexes in human malignancies. The title of the EvansMDS grant is: "Cryo-Electron Microscopy Structures of Mutant U2AF1-Containing Ribonucleoproteins Associated with Myelodysplastic Syndromes". This grant was made possible by our new Talos cryo-EM.

The Mathews and Ermolenko labs have recently showed that RNAs universally fold into secondary structures with short end-to-end distances. In this new article, possible roles of the inherent mRNA compactness in translation and mRNA decay are reviewed.

While other cancer researchers had to temporarily close their labs in March due to the COVID-19 pandemic, Isaac Harris, Ph.D., and Josh Munger, Ph.D., shifted their focus to the contagion that has reshaped the world.

Using their specialized knowledge of viruses and genomics technology at the Wilmot Cancer Institute, the duo is searching for new and existing, U.S Food and Drug Administration-approved medications that could block the coronavirus.

They've tested 624 drugs on thousands of human lung cells infected with a strain of the coronavirus to see if the drugs have any impact. So far, they've discovered 15 potential compounds that appear to have anti-viral activity. Their criteria for a "hit" is for the drug to block 50 percent of virus-induced cell death. The team is validating the 15 drugs and trying to understand the mechanisms behind their potential anti-viral activity, Harris said.

This type of research is known as high-throughput drug screening -- a process that plays a big role in drug discovery in modern medicine. But instead of finding a new drug, here, investigators are looking to repurpose existing, available drugs for treatment of the coronavirus. This involves using automated, robotic equipment to match drug candidates with cellular events that occur during disease transformation. This form of drug-screening is often less expensive and faster than developing treatments from scratch.

Chen Bao

In a new paper just published in the journal eLife, the Ermolenko lab in collaboration with the Grigorieff lab at HHMI uncovers the underlying mechanism by which secondary structure in mRNA causes ribosome pausing. Specifically they show that mRNA stem-loops can cause translation pausing by inhibiting binding of tRNAs to the A site of the ribosome. The lead author on the work is Chen Bao, a Biochemistry graduate student. The work was funded by NIH.

Congratulations to Chapin Cavender and Michael Bryan for winning University of Rochester's Hooker Fellowships, recognizing their achievements in their thesis research. Chapin and Michael are Biophysics students working in the labs of David Mathews and Ben Miller, respectively.

Michael Bryan

Chapin Cavender

This week's URMC Research Heroes featured the Maquat lab's Tatsuaki Kurosaki, PhD, and Shuhei Mitsutomi, MS, who were recognized today for their work on SARS-CoV-2.

https://www.instagram.com/p/CA-QN7oAl07/

Both Tatsuaki and Shuhei have worked as members of the Maquat Lab (Center for RNA Biology and the Department of Biochemistry & Biophysics) during the sequestration on SARS-CoV-2, collaborating with a lab at Harvard to determine the mechanism by which the virus inhibits human-cell nonsense-mediated mRNA decay (NMD) so as to express and replicate its RNA efficiency.

From Tatsuaki: "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 19 (COVID-19) pandemic, is a novel enveloped RNA virus carrying a large (~30 kb) positive-sense single-stranded RNA genome. Although human cells innately have an RNA surveillance pathway called nonsense-mediated mRNA decay (NMD) that generally protects cells from infection by many different types of viruses, little is known about how SARS-CoV-2 inhibits NMD to proliferate in human cells. We hope that our research helps to elucidate the molecular mechanisms of SARS-CoV-2 proliferation in human cells, eventually contributing toward the development of therapeutic strategies to combat COVID-19."

Sponsored by the RNA Society & Lexogen, UR RNA Structure & Function Cluster, and UR Center for RNA Biology

Who is eligible: Any University of Rochester graduate student or post-doc with an interest in RNA biology

Entry rules: Essays should be no more than two pages, single-spaced (excluding references, which should be present), 11-point Arial font, with half-inch margins all around.

Prizes: Two prizes will be given out. Gold (valued at ~$1000), and Silver (valued at ~$250). Additionally, winning essays along with photos of the winning authors will be posted on the Center for RNA Biology webpage and featured on the RNA Society's RNA Salon page, offering international exposure.

Details

The UR's Center for RNA Biology is running an essay contest, sponsored by the RNA Society & Lexogen, and UR's RNA Structure & Function Cluster, on "The role of RNA research in community health". This contest, which is open to all UR graduate students and post-docs, aims to promote creative yet data-driven thinking about the importance of RNA in the "big picture".

Considering that reliable technology is required for research in an increasingly virtual world, prizes will consist of a PC or Mac laptop for Gold winners (~$1000), and software licenses or peripherals (e.g., second monitor or laptop dock) for Silver winners (~$250), subject to the needs of each recipient.

Submissions must be emailed to Liz by Monday, July 13th, 2020.

Winners will be announced in the beginning of August.

Links

The RNA Society: https://www.rnasociety.org/

RNA Structure & Function Cluster: http://www.rochester.edu/ucis/rnastructure.html

Center for RNA Biology: https://www.urmc.rochester.edu/rna-biology.aspx

PALMYRA, NEW JERSEY: New biochemistry doctoral graduates Chris Goodwin and Sierra Fox celebrate at home.

Chris Goodwin and his wife, Sierra Fox, received their doctoral degrees in biochemistry from the School of Medicine. They met at the University years ago and both received master's degrees in 2016. They celebrate Friday at their home in Palmyra, New Jersey. "Going from grad school into quarantine has been very weird," Goodwin says.

They celebrated by baking cinnamon buns and eating them while they watched the online commencement videos and the School of Medicine and Dentistry biochemistry and biophysics department virtual award ceremony. "We had a 'Sierra and Chris' banner left over from our post-thesis defense party months ago and hung that up behind us for a more festive atmosphere," Goodwin says.

On Friday May 15th, the department held it's first virtual awards ceremony. Please see the video below:

Congratulations to all of our graduates:

Ph.D. Program in Biochemistry

Meemanage (Dudarshika) De Zoysa
Sierra Fox
Christopher Goodwin
Wan-Jung (Christine) Lai
Jiyu Wang
Hong Zhu

Ph.D. Program in Biophysics

Debapratim (Dave) Dutta
Letty Leslie Salas-Estrada

Congratulations to our 2020 award winners:

Walter S. Bloor Award
For excellence of the Ph.D. thesis and in the research leading to the dissertation in the Program in Biochemistry

Christopher Goodwin, Jiyu Wang

Marvel-Dare F. Nutting Award In recognition of an outstanding graduate receiving a Ph.D. in Biochemistry

Hong Zhu

George V. Metzger Award For excellence of the Ph.D. thesis and in the research leading to the dissertation in the Program in Biophysics

Leslie Salas-Estrada

Fred Sherman Award Program in Biochemistry award to a student who exemplifies the imagination, the excellence in the pursuit of scientific knowledge, and the commitment to the scientific community that were characteristic of Dr. Fred Sherman

Lisa Houston, Nazish Jeffery

William F. Neuman Award Program in Biophysics award for academic, scientific and personal qualities exemplifying the imagination, enthusiasm and excellence in the pursuit of scientific knowledge which were characteristic of the life of Dr. Neuman

Dan Steiner

William F. & Margaret W. Neuman Travel Award

Lauren Benoodt, Ashlin Poruthoor, Yoshita Srivastava

Elena Gilde Grossfield Biophysics Trainee Presentation Award

Talk -- Matt Brewer

Poster -- Gabrielle Kosoy

Dr. Mark Dumont, Advisor. Awarded by the Department of Biochemistry.

Marvel-Dare Fellows Nutting was the first woman to receive the Ph.D. in Biochemistry at the University of Rochester, June 1938. Her thesis, The Anti-Gonado Trophic Hormones in the Normal Blood Serum reflected the interests of Dr. Arthur Elden, Professor of Obstetrics and Gynecology and Dr. Willard Allen, Professor of Anatomy. Prior to beginning the Ph.D., she had worked with Professor Bloor, the first Chairman of Biochemistry and Dr. William McCann, Chair of the Department of Medicine. After time extending her thesis work, she took a position in Washington, DC as a Medical School faculty member, teaching biochemistry to students in the V-12 Program (an accelerated M.D. program designed to provide doctors for World War II)

In 1947, she began a career in the Department of Agriculture in California as an Associate Biochemist, with a focus on vitamins in vegetables, including frozen foods being developed at that time. A specific interest was Vitamin C in tomatoes and in this work she developed photometric and other technology for analysis. She headed a research group in food appraisal and statistics. An avid athlete she remained active in sports until her death in 2005.

She donated her hood from the 1938 graduation ceremony as her means of honoring women graduates in the Department of Biochemistry. In addition she has contributed funds to support the Nutting Student Travel Award as well as for the award associated with the Nutting Hood.

In 2004, at age 94 when the Nutting Hood Award was established, Dr. Nutting wrote:

"Words are inadequate to express my deep and sincere feeling of awe and humbleness in this matter. I can only ask you to extend my great thanks to everyone involved in this unexpected honor with its further extension into other years. I am convinced my thanks are in no way equal to these happenings. They are from the bottom of my heart".

Hong Zhu's thesis project focused on the identification of variant forms of the HIV envelope protein for use in HIV vaccine development. Dr. Zhu initially helped to establish a technology for displaying and detecting the envelope protein on the surface of yeast cells as a system allowing the protein to be subjected to in vitro evolution. Since poor binding of envelope protein to antibody precursors appears to be a major barrier to the elicitation of neutralizing responses to potential HIV vaccines, Dr. Zhu used large-scale random mutagenesis and extensive screening by flow cytometry to identify variant forms of the envelope that exhibit enhanced binding to precursor forms of broadly neutralizing anti-HIV antibodies. The variant forms of the envelope that she identified are likely to be trapped in conformational states that allow enhanced access for antibody binding. While performing this work, Dr. Zhu also completed coursework allowing her to receive a Master of Science Degree in Technical Entrepreneurship and Management jointly from the Simon Business School and the Hajim School of Engineering and Applied Sciences. While conducting her Ph.D. research, she also served as a consultant for Estée Lauder Inc.

Congratulations to Viktoriya Anokhina who was elected as a co-chair of the Gordon Research Seminar Nucleosides, Nucleotides and Oligonucleotides, to be held in 2021. The Gordon Research Seminar is a 2-day meeting that precedes a Gordon Research Conference. These seminars are organized by early-career scientists for trainees of all levels and junior scientists. Some of Viktoriya's responsibilities as a co-chair will include Keynote speaker selection and invitation, career panel participants invitations, fundraising, selection of speakers from submitted abstracts, and other organizational activities. To attend the 2019 meeting, Viktoriya was supported by the Sayeeda Zain and Graduate Women in Sciences travel awards.

Viruses like the coronavirus that causes COVID-19 are able to unleash their fury because of a devious weapon: ribonucleic acid, also known as RNA.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. As COVID-19 continues to spread around the globe, RNA research provides an important foundation for developing antiviral drugs, vaccines, and other therapeutics to disrupt the virus and stop infections.

"Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA does—make new virus that can infect more of our cells and also the cells of other human beings," says Lynne Maquat, professor of biochemistry and biophysics at the University of Rochester Medical Center and the director of Rochester's Center for RNA Biology.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, "the RNA research world has exploded," Maquat says. "The University of Rochester understood this."

In 2007, Maquat founded the Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

While much of the research across the University has been put on pause, labs that are involved in coronavirus research remain active.

"Our strength as a university is our diversity of research expertise, combined with our highly collaborative nature," says Dragony Fu, an assistant professor of biology on the River Campus and a member of the Center for RNA Biology. "We are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics."

Biochemistry and Biophysics grad students and post docs Jessica Ciela (Munger Lab), Dan Steiner (Miller Lab), Joe Bucukovski (Miller Lab), and Morgan Monaghan, PhD (Munger Lab) were all featured in the Grad student appreciation week article this month. Congrats to them and keep up the amazing research!

A vaccine for COVID-19 is likely years away. Yet a drug tested in a lab three weeks ago has been found to stop the virus from spreading from cell to cell.

The stunning announcement comes from a Rochester biotech company called OyaGen, Inc. The company is seeking to fast-track the formula to treat people who become infected.

"A treatment right now is the priority," said Dr. Harold Smith of OyaGen. He added the drug already has FDA approval for another use.

The tests were conducted at the federal government's integrated research facility in Fort Detrick, Md. A drug called Oya 1 had already been proven in lab tests there to be effective against Ebola.

"If it worked for Ebola, is it absolutely unique to Ebola, or would it work on other viruses?" asked Dr. Smith - though he said an actual drug for human consumption was never pursued.

The coronavirus was still new and contained to Wuhan, China when a sample of the live virus was shipped to the government lab for testing with Oya 1. Test samples viewed under a microscope show a clear "before" and "after" that indicates properties that allowed the virus to grow and spread were neutralized.

"The drug was so effective that, even though we got through our dose-testing, we had literally sterilized the culture of the virus, so we knew this was a powerful thing," said Dr. Smith.

Under a different name, Oya-1 was first developed in the 1960s as a treatment for cancer. It was later shelved as ineffective, but not before it received approval from the Food and Drug Administration. Safe dosage levels were determined for men, women and children.

"Clinical trials have already been done on this compound and, if safety is a main issue, we feel safety has been addressed years ago," said Dr. Smith.

He said preliminary research indicates a single dose of the medicine stops the progression of COVID-19 for eight days and continues to work at half-strength for another four days.

The question is whether the drug will react to the virus the same way in the body as it has in the lab. When an approved drug is proposed for a new use, the FDA usually requires new clinical trials.

13WHAM News reached out to the FDA, but we have not yet received a response.

OyaGen says the live virus tests were conducted and validated by a third party - the U-S government, and argue that is also a reason the drug should be fast-tracked.

"You've got this compound that's absolutely lethal to the virus, and we know it has a margin of safety in people," said Dr. Smith. "What are we waiting for?"

Professor You was quoted in a Nature review article published February 4th, 2020, entitled Step Aside CRISPR, RNA Editing Is Taking Off. Dr. Yu stated that a large number of genetic diseases are the result of mutations leading to stop codons, resulting in a shortened protein that doesn't function normally in the body. He noted that the list of such diseases is very long and includes cystic fibrosis, the eye disease Hurler's syndrome, and numerous cancers. On February 6th, Dr. Yu was notified that he had won a major grand award from the Cystic Fibrosis Foundation entitled "CFTR nonsense suppression by targeted pseudouridylation." Congratulations to Dr. Yu!

Harold Smith, Ph.D., Professor of Biochemistry and Biophysics, will serve as Chair and organizer for the 5th Annual International Preclinical Drug Discovery Conference to be held November 21-23, 2019 in Boston. Dr. Smith will also speak at the conference, and several other University of Rochester students, postdocs and faculty will also participate. The link to the meeting can be found her: https://unitedscientificgroup.com/conferences/drug-discovery/pdfs/DrugDiscovery-2019_Program.pdf

Lynne Maquat, Ph.D., the J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics, was honored with the International Union of Biochemistry and Molecular Biology (IUBMB) Jubilee Lectureship in September. The IUBMB unites biochemists and molecular biologists in 75 countries and is devoted to promoting research and education in biochemistry and molecular biology, giving particular attention to areas where the subject is still in its early development.

The IUBMB Jubilee Lectureship was established to commemorate the 50th anniversary of the First International Congress of Biochemistry that was held in Cambridge, England in 1949, at which the initial steps were taken that led to the formation of IUBMB. Maquat gave the keynote lecture at the IUBMB Molecular Biosystems Conference in Puerto Varas, Chile on September 30 and was presented with a medal in recognition of the event.

The founding director of the University of Rochester's Center for RNA Biology, Maquat has spent her career deciphering the many roles that RNA plays in sickness and in health. She's an international leader in the field and is credited with several major discoveries that are informing a new generation of therapies for a wide range of genetic disorders.

Her lecture, titled "Nonsense-mediated mRNA Decay in Human Health and Disease," described her discovery of nonsense-mediated mRNA decay or NMD and how this important surveillance system protects against mistakes in gene expression that lead to disease. She also discussed ongoing work on how misregulation of NMD in Fragile X Syndrome, the most common single gene cause of intellectual disability and autism, results in neuronal defects that typify this disorder.

Peng Yao, Ph.D., an Assistant Professor in the Department of Medicine, CVRI and a member of the Biochemistry and Molecular Biology Graduate Program co-organized the 2019 Rustbelt RNA Meeting with Drs. Hua Lou and Jo Ann Wise of Case Western Reserve University. The conference, with approximately 400 attendees was held on October 25th & 26th, at Case Western University and featured 25 speakers, including a workshop on "Using CRISPR-Cas13 to target and detect RNA" by Dr. Mitch O'Connell and talk or poster presentations by laboratory members from the labs of Drs. Charles Thornton, Dragony Fu, and Peng Yao. BMB Students Omar Hedaya and Feng Jiang helped design and construct the meeting booklet and organize the meeting. The meeting was supported by the University of Rochester Center for RNA Biology and the Department of Biochemistry and Biophysics, among 19 other departments, 10 industrial vendors, and 5 journals/societies.

UR trainees who presented a talk or poster at the 2019 RBR Meeting

Jenna M. Lentini (graduate student from Dragony Fu lab) gave a talk and won an outstanding presentation award for graduate students.

Kejia Zhang (graduate student from Dragony Fu lab) gave a poster presentation.

Matthew Tanner (graduate student from Charles Thornton lab) gave a poster presentation.

Kadiam C Venkata Subbaiah (postdoctoral fellow from Peng Yao lab) gave a talk.

Jiangbin Wu (postdoctoral fellow from Peng Yao lab) gave a poster presentation.

On July 29, Chris Goodwin successfully defended his thesis, "The intersection of Human Cytomegalovirus infection and innate immune signaling", thereby obtaining his Ph.D. Chris found that the cellular IKK kinases limit the ability of Human Cytomegalovirus to initiate infection. Further, he found that the Human Cytomegalovirus UL26 protein prevents IKKB from inducing the expression of anti-viral interferon stimulated genes. Chris' work sheds new light on the measures and counter-measures taken by viruses and host cells to try to control the outcome of infection. Chris was mentored by Joshua Munger, and was awarded the Fred Sherman Biochemistry Award, the URBest Sharing Science Video Communication Award, and the Biochemistry Student Seminar Award. Good luck as you embark on your independent career Chris!

Brandon Berry, a Ph.D. Student in the Molecular Pharmacology and Physiology Ph.D. program, and an appointee to the NIH T32 Training Grant in Cellular, Biochemical, and Molecular Sciences, wrote an insightful essay on "Balancing Criticism and Confidence" in graduate school, which was posted on the Career Stories@URBest website. The essay can be found here: https://www.urmc.rochester.edu/education/graduate/ur-best-blog/july-2019-1/balancing-criticism-and-confidence.aspx.

On July 19, Dalia Ghoneim earned her Ph.D. for successfully defending her thesis, "New functions for RNA elucidated by evolutionary conservation." She demonstrated that adjacent pairs of codons known to inhibit protein expression and to slow translation in yeast are conserved, rather than avoided. Genes with these conserved codon pairs exhibit altered translation properties. Thus, conservation is evidence that these codon pairs serve a function in yeast, although that function is yet to be determined. Additionally, in collaboration with Xin Li's lab, Dalia scanned mouse sperm transcriptome data using a machine learning method to identify sets of long-non-coding RNAs with conserved structures. Dalia was mentored by David H. Mathews and Beth Grayhack. During her studies, Dalia was awarded the prestigious Perricone MD Born Seekers fellowship. We wish Dalia all the best for her post-doctoral career!

Professor Russ Hilf celebrated 50 years of service at the University of Rochester Medical Center on June 19th, 2019, by presenting an overview of his life, career and scientific accomplishments. He was also presented with a plaque commemorating his 50 years of service to the University from the Department of Biochemistry and Biophysics. Dr. Hilf's first appointment, as an Associate Professor, began July 1, 1969.

Dr. Hilf receives the commemorative plaque from Jeff Hayes, Chair of the Department of Biochemistry and Biophysics.

So what exactly happens inside your body when you consume Cannabis? Dr. Smith outlines the powerful role of the Endocannabinoid System in modulating human health, and discusses the future of Cannabis research and testing.

The Born Seekers fellowship is a speech contest that is open to women in STEM. The work they do pushes boundaries and meaningfully impacts society on a local, national, and often global level. The women selected as our 2019 Born Seekers build skills in communication and leadership, serving as role models for the next generation of scientists, engineers, doctors, and STEM professionals.

Dalia Ghoneim is a PhD candidate in Genetics at the University of Rochester in Rochester, NY. She develops and contributes to software that helps us understand the structure and functions of genetic molecules, and has worked to analyze mutations in DNA from patients with severe neurological diseases like epilepsy and autism. This work was instrumental to identifying new genes that cause these diseases. Dalia takes as many opportunities as she can to share science with others by participating in outreach and advocating for inclusion in science. Outside of science, Dalia is a single mother to four wonderful children, a competitive runner, and enjoys figure drawing and learning and experiencing new things.

The Departments of Biomedical Genetics and Biology, with the support of the University Committee for Interdisciplinary Studies, host the 31st annual Genetics Day Symposium on Thursday, April 25, from 9:30 a.m. to 4 p.m. in the Class of '62 Auditorium and Flaum Atrium. This year's Fred Sherman Lecturer will be Phillip Zamore, a Howard Hughes Medical Institute investigator and professor of biomedical sciences at the University of Massachusetts Medical School, giving a talk titled "piRNAs and the Struggle to Reproduce."

Dr. Rubin describes his own battle with prostate cancer, and how as a scientist how he took control of his own treatment. He also describes the impact of personalized medicine on his medical decisions and how he deals with living with cancer. Read the article.

Jerry Madukwe, Ph.D., who received his Ph.D. in Biochemistry (2018), and is currently a postdoctoral fellow at Yale University, recently completed a 2-week science-outreach trip to West Africa. Jerry was invited by the West Africa Center for Cell Biology of Infectious Pathogens at the University of Ghana, and the Department of Life sciences at the University of Ilorin in central Nigeria to talk about the work he did as a PhD student and about graduate school in the United States. Jerry, who hails from Nigeria, and got his BS from Lee University in Tennessee, also used the opportunity to visit his former elementary school where he talked to fifth grade pupils about science (see photos), and to demonstrate DNA extraction from bananas. The kids were very excited by his visit, and Jerry found the experience very fulfilling.

The department is pleased to announce the winners of the Sayeeda Zain Fall Travel awards: Shashank Chavali, Tyler Couch, Meemanage Dudarshika DeZoysa and Fanfan Hao.

The Sayeeda Zain Travel Award honors the distinguished career and charitable life of Dr. Sayeeda Zain. The award is given in recognition of research excellence to support travel and related expenses associated with attendance at a scientific conference or corporate internship to gain practical experience. The next round of Sayeeda Zain Travel Awards will be offered in Spring 2019.

Thank you to all those who applied and congratulations to Shashank, Tyler, Dudarshika and Fanfan!

Harold C. Smith was a guest along with Bob Duffy (CEO of the Greater Rochester Chamber of Commerce), Jason Klimek (attorney with Boylan Code), Zachary Sarkis (co-founder of Flower City Solutions) and Jacob Fox (founder of Closed Loop Systems) on WXXI Connections with Evan Dawson on 11/21/2018 to address the opportunities and questions surround the emerging hemp industry in Up State NY. (listen to Hemp101http://www.wxxinews.org/programs/connections?page=1&ajax=1)

Dr. Smith spoke regarding the future of labeling and dosing of THC-free and THC-containing products relative to what we understanding from scientific and clinical research. Having founded CannaMetrix, LLC, a New York based company, Dr. Smith seeks to establish through patent pending, cell-based assays, to raise the standards for product development and quality control so as to better information patient choices of products containing full spectrum plant cannabinoids or synthetic cannabinoids and advance medicinal use of cannabis.

Highlights of Session 1.1.2 on Nucleic Acid were reported in ACA RefleXions Fall 2018 and provided many new insights into the form and function of nucleic acids and was co-organized by Dr. Joseph Wedekind and Dr. Rui Zhao. Dr. Wen Zhang of Harvard University presented mechanistic studies of non-enzymatic RNA polymerization using custom phosphoramidites with imidazole leaving groups that were caught in the act of catalysis by crystallographic snapshots. This work has implications for catalysis in a pre-biotic RNA world. Sun Cheol Park from Kangwon National University, Korea described DNA recognition by the PadR repressor. Binding of phenolic acid blocks DNA binding to relieve PadR repression, activating downstream detoxification genes. Dr. Yun-Xing Wang from NIH/NCI described use of an X-ray free electron laser to capture conformational changes of the adenine riboswitch during effector binding, providing insights into RNA-mediated translational regulation.

Prof. Clara Kielkopf from the University of Rochester described progress to decode the basis of 3´-splice site recognition of pre-mRNA by U2AF proteins, including polypyrimidine tract recognition and binding to degenerate splice-sites. The work has implications for correction of splicing defects found in human diseases. Dr. Eric Montemayor from the University of Wisconsin described later steps of pre-mRNA splicing, including a model for U6 snRNA remodeling by contacts to the Lsm2-8 ring protein and the Prp24 chaperone. Dr. Soumya Remesh from the Lawrence Berkeley National Lab used small angle scattering and soft X-ray tomography to reveal how small molecules interact with the abundant HU protein to alter DNA supercoiling. The work has implications for controlling bacterial gene expression. The session was anchored by Dr. Ailong Ke of Cornell University who presented structural snapshots that contribute a novel mechanistic framework to describe how bacterial type II-A CRISPR systems create new molecular memories of short, foreign 'spacer' DNAs that invade bacterial cells.

Biochemistry professor Mark Dumont, Ph.D. is the recipient of the 2018 Outstanding Graduate Student Teacher Award. Established in 2013, this award is given to an outstanding graduate student teacher for record of excellence in classroom instruction. Mark was nominated by graduate students Brandon Davis, Ashwin Kumar and Matthew Raymonda.

This award was presented at the School of Medicine and Dentistry Convocation Ceremony, September 6, 2018.

The department would like to extend congratulations to Mark on this well- deserved honor.

The department would like to thank all that participated in the BCBP Halloween Door Contest this year!

This year the winner is…

The Kielkopf Lab!!

Tied for second place are the Ermolenko Lab and the Grossfield Lab! Congratulations to everyone – the doors looked awesome!

Lynne Maquat, PhD, was inducted into the National Academy of Medicine (NAM) on Saturday October 13th in Washington, DC. Here, she is receiving her diploma and congratulations from Victor Dzau, MD, President of NAM after being introduced by J. Michael McGinnis, MD, the Executive Officer of NAM.

Myelodysplastic Syndromes (MDS) are a group of diverse bone marrow disorders, in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a “bone marrow failure disorder.”

Congratulations, Clara and her lab!

The Department of Biochemistry and Biophysics has loaned a statue of J. Robert Oppenheimer and Albert Einstein to the Laboratory of Laser Energetics. The sculpture was commissioned by the Department of Radiation Biology and Biophysics (William Neuman and Aser Rothstein co-chairs) in October of 1968 and was crafted by Achille Forgione, a notable Rochester artist. The work was in place by the fall of 1970, originally at the entrance to the OO wing, then moved to the Blair Library (no longer in existence). The statue has been in the back of the Neuman Room for many years. It is now displayed prominently in the LLE lobby. An engraved plate will be placed next to the statue, reading: "Albert Einstein, J. Robert Oppenheimer, Statue commissioned by Dr. William "Bill" Newman, On loan from the University of Rochester's Department of Biochemistry and Biophysics"

For more information on Dr. Neuman and his work please visit our department featured alumni page.

<p>The Department of Biochemistry and Biophysics has loaned a statue of J. Robert Oppenheimer and Albert Einstein to the Laboratory of Laser Energetics. The sculpture was commissioned by the Department of Radiation Biology and Biophysics (William Neuman and Aser Rothstein co-chairs) in October of 1968 and was crafted by Achille Forgione, a notable Rochester artist. The work was in place by the fall of 1970, originally at the entrance to the OO wing, then moved to the Blair Library (no longer in existence). The statue has been in the back of the Neuman Room for many years. It is now displayed prominently in the LLE lobby. An engraved plate will be placed next to the statue, reading: "Albert Einstein, J. Robert Oppenheimer, Statue commissioned by Dr. William "Bill" Newman, On loan from the University of Rochester's Department of Biochemistry and Biophysics"</p><p>For more information on Dr. Neuman and his work please visit our department <a href="https://www.urmc.rochester.edu/biochemistry-biophysics/people/featured-alumni.aspx#Neuman">featured alumi page</a>.</p> <div class="image-caption full-size no-border"> <img alt="Neuman statue" class="imgFrame" src="https://www.urmc.rochester.edu/neuroscience/_shared/News/2750/Neuman.jpg" /> <p class="captionCenter"> </p>

Co-crystal structure of HIV trans-activation response (TAR) RNA (rainbow ribbon) in complex with lab-evolved protein, TBP6.7 (blue Cα ribbon). A short peptide (pink) binds TAR outside the context of TBP6.7. (art by Joseph Wedekind). The underlying electron micrograph shows HIV virions (CDC image #13472 by Maureen Metcalfe and Tom Hodge).

Nucleic Acids Research Breakthrough article describes structure of HIV TAR complex with engineered binding protein and structure-based synthesis of antagonist

Investigators at multiple research institutes, led by Dr. Joseph Wedekind (University of Rochester) have described the high resolution crystal structure of a laboratory-evolved protein bound to its tightly associated HIV TAR RNA target, and subsequent synthesis and characterization of a stapled peptide mimic of the predominant RNA binding epitope in that protein. The study provided a detailed framework for peptide-mediated TAR recognition that might be generally applicable to target other disease-relevant RNAs.

HIV/AIDS is a global health threat that requires new insights into viral targets, especially those that resist mutation and promote novel aspects of the viral life cycle. In these respects, the HIV-1 trans-activation response (TAR) RNA is of ongoing interest. Previously, investigators (including some from this author group) developed methods to produce a unique lab-evolved protein ('TBP6.7') that recognizes TAR with extraordinarily high affinity compared to known TAR binders [Crawford et al. McNaughton (2016) ACS Chem. Biol. 8, 2206]. However, the molecular determinants of TAR recognition remained obscure, thus limiting the investigators' ability to further exploit that discovery. The crystal structure of this complex allowed investigators to determine that only a subset of the 'evolved' protein sequences are actually involved in RNA binding, with the preponderance of interactions localized to a short β-hairpin. This observation led them to synthesize a short, stapled peptide that mimics the β-hairpin and attenuates TAR-dependent transcription in HeLa nuclear lysate.

The study reported here [Belashov et al. Wedekind (2018) Nucleic Acids Res. 46, 6401-6415] is highly multi-disciplinary, spanning crystallography, site-directed mutagenesis, calorimetry, cell-surface display, ELISA, transcription assays, molecular dynamics simulations, and constrained peptide synthesis. In the end, the conversion of the parental RNA binding protein from single- to double-stranded RNA recognition implies that the protein has sufficient plasticity to recognize numerous RNA folds.

Reviewers and editors familiar with the work have stated that the study is "a strong contribution to a difficult field" that "will have substantial impact in the field of RNA recognition, ranging from applied (specifically targeting therapeutically relevant RNAs) to basic (understanding how RRMs bind to specific RNAs in the cell)"

The Wedekind laboratory at the University of Rochester investigates the mechanisms of action of non-protein-coding (nc)RNAs, and is interested especially in the three-dimensional architectures of these RNAs and how they bind to specific small molecules or peptides, leading to conformations that alter biological function. The research was supported by the University of Rochester Center for AIDS Research, and the National Institutes of Health.

By Dr. Joseph Wedekind

The Department of Biochemistry & Biophysics is pleased to announce the winners of the Sayeeda Zain Fall Travel awards: Debapratim Dutta, Sierra Fox and Hong Zhu.

The Sayeeda Zain Travel Award honors the distinguished career and charitable life of Dr. Sayeeda Zain. The award is given in recognition of research excellence to support travel and related expenses associated with attendance at a scientific conference or corporate internship to gain practical experience.

Debapratim (Dave) Dutta is presenting a poster and was invited to give a talk at the Annual RNA Society Meeting (Berkeley, CA). Sierra Fox presented a poster and was a Keystone Symposia Future of Science Fund Scholarship recipient at the Keystone Symposia in Chromatin Architecture and Chromatin Organization, and Gene Control in Development and Disease Symposia (Whistler, BC, Canada). Hong Zhu presented a poster at the III International Conference on Vaccines Research and Development (Washington, DC).

Pictured are Anne Cheng, Venice Magunga, and Anmol Almast following the Arts, Sciences & Engineering commencement ceremony Sunday. Photo reproduced from 5-21-18 issue of @Rochester

The Department of Biochemistry and Biophysics congratulates the 20 young men and women who received their B.S. in Biochemistry this weekend. We look forward to their continued success in their future training and careers! In addition to the University-wide celebration, these graduates received their diplomas at a ceremony in The Class of ’62 Auditorium, attended by their families, friends, and faculty from the many departments involved in their training. The ceremony was officiated by Beth Grayhack, Ph.D., Director of the Undergraduate Program (Biochemistry and Biophysics), and was enriched by addresses from Sina Ghaemmaghami, Ph.D. (Biology) and Mark Dumont (Biochemistry and Biophysics).

On Friday May, 18th the department held it's annual awards ceremony in the Neuman Room. At the event this year the following awards were awarded to our current B&B graduate students:

• Bloor Award - Christina Brule and Lu Han
• Metzger Award - Karl J. P. Smith
• Sherman Award – Bronwyn Lucas
• Neuman Award – Chapin Cavender
• Grossfield Award – Sreyoshi Sur (talk), Lauren Benoodt (poster)
• Student Seminar Award – Fall: Bronwyn Lucas (BMB), Leslie Salas-Estrada (BSCB)
  Spring: Viktoriya Anokhina (BMB), Daniel Steiner (BSCB)
• Hooker Award – Dudarshika DeZoysa (BMB), Christina Lai (BMB)
• Goodman Fellowship (3rd place for the Messersmith Award) – Leslie Salas-Estrada
• Faculty Award – Mark Dumont (BMB), Alan Grossfield (BSCB)
• Zain Award – Christine Lai, Lingfeng Luo, Louis Smith

Congratulations to all the winners and our 2018 graduates!

View photos from the event.

Scientists have begun to implicate extracellular vesicles and exosomes in everything from cancer to viral infections to basic neural functioning. To Lynne Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor in the Department of Biochemistry and Biophysics, the process shows how parts of the genome we used to think of as junk actually have important functions. “You could say that the host domesticated a viral sequence for its own purposes,” Maquat says. “That’s the beauty of our complexity—[these elements] allow tinkering or fine-tuning of genes.”

The magazine's new issue, now in an interactive, flip-book format, highlights the investigative work of the J. Lowell Orbison Endowed Chair, as well as the impressive efforts of our medical students, alumni and faculty—past and present.

Lynne Maquat, PhD, received the 2018 Federation of American Societies for Experimental Biology (FASEB) Excellence in Science Award during the Experimental Biology 2018 meeting in San Diego, hosted by the American Society for Biochemistry and Molecular Biology (ASBMB). The award recognizes women whose outstanding career achievements in biological science have contributed significantly to the understanding of a particular discipline through scientific achievements, training of students and postdoctoral fellows, and contributions to the broader scientific community. Maquat is best known for unraveling RNA's role in sickness and in health and for advocating for young women in the sciences. View Dr. Maquat's award interview on ASBMB's interviews page.

Read more: Maquat celebrated for her service and scientific achievements
Read more: Unraveling RNA and Stereotypes: Q&A with award-Winning Scientist Lynne Maquat

Cancer is a group of diseases in which the body's cells divide uncontrollably and invade nearby tissues. Scientists at Wilmot Cancer Institute and the University of Rochester's Center for RNA Biology are working to understand more about how and why this happens.

One piece of the puzzle they're studying is ribonucleic acid, or RNA, which is found in all cells. RNA is made in the nucleus of a cell from our DNA, which holds the instruction manual for life. RNA puts those instructions into action.

RNA comes in many forms. One form, called messenger RNA (mRNA), carries those instructions out of the nucleus to the ribosomes, where proteins are made. These proteins are essential for functions ranging from digestion to protecting us from disease. If the mRNA has a bad copy of instructions, then either a faulty protein or no protein is created, leading to diseases like cancer.

Understanding the quality-control system

Lynne E. Maquat, Ph.D., director of the Center for RNA Biology, studies a quality control process that blocks cells from making faulty proteins. Called nonsense-mediated mRNA decay (NMD), this process comes into play when mRNA has a set of instructions with a mistake that will lead to short or incomplete proteins. NMD acts like a set of factory inspectors that find and destroy this mRNA before the faulty proteins can be made.

Sometimes, though, NMD doesn't catch the mistakes and harmful proteins are made. This process plays a part in one-third of all inherited diseases, such as cystic fibrosis and muscular dystrophy, and one-third of all acquired diseases, including a number of cancers.

One reason is that tumors can influence how these inspectors work. Maquat and her team are looking for ways to stop tumors from interfering with NMD with the goal of finding new ways to treat cancer.

Slowing cancer's growth

A team from Maquat's lab has also identified a protein called Tudor-SN that is important as cells prepare to divide. This protein controls many microRNAs, molecules that are very small RNAs that control the expression of tens of thousands of genes.

The scientists found that when Tudor-SN is removed from human cells, levels of hundreds of microRNAs go up, putting the brakes on genes that encourage cell growth. This slows down the process of cell division known as the cell cycle, which goes awry in cancer.

Maquat and Reyad A. Elbarbary, Ph.D., a former post-doctoral fellow in Maquat's lab, have filed a patent application for methods that target Tudor-SN for the treatment and prevention of cancer. They continue to study how Tudor-SN works in concert with other molecules and proteins so that scientists can identify the most appropriate drugs to target it.

Other avenues

Scientists at the Center for RNA Biology are also looking at RNA's other roles in cancer to find new treatment strategies. For example, Mitchell O'Connell, Ph.D., is studying how microRNAs can interfere with the way genes are expressed and lead to cancer. He and his team are using the gene-editing technology known as CRISPR, which he has adapted to edit RNA, to learn more about the proteins involved in this process.

Yi-Tao Yu, Ph.D., and his team are studying various ways to modify mRNA so that it can override mistakes in genetic instructions. Sometimes there's a premature stop signal that orders a cell to stop reading the genetic instructions in mRNA partway through the process, resulting in an incomplete protein. The Yu lab is working to alter mRNA in ways that turn "stop" signals into "go" signals, creating full length proteins and preventing diseases like cancer.

The study of RNA biology is allowing scientists and physicians to explore entirely new treatment strategies for cancer and a wide range of other genetic and acquired disorders.

Learn more about the work being done at the Center for RNA Biology.

By Lydia Fernandez

The Wiley Foundation today announced the 17th annual Wiley Prize in Biomedical Sciences will be awarded to Lynne E. Maquat for elucidating the mechanism of nonsense-mediated messenger RNA decay, a fundamental process whereby cells remove defective transcripts that can encode toxic proteins.

Dr. Maquat is a Professor at the Department of Biochemistry & Biophysics in the School of Medicine and Dentistry, the Founding Director of the Center for RNA Biology: From Genome to Therapeutics, the Founding Chair of the University of Rochester Graduate Women in Science, and the J. Lowell Orbison Endowed Chair at the University of Rochester in Rochester, New York.

"The 2018 Wiley Prize honors Dr. Maquat, whose work illuminated how our cells prevent production of toxic proteins by removing defective messenger RNAs," said Dr. Titia de Lange, chairperson of the awards jury for the Wiley Prize at the Rockefeller University in New York City.

"The Wiley Foundation honors research that champions novel approaches and challenges accepted thinking in the biomedical sciences. The work of the 2018 Wiley Prize recipient Lynne Maquat truly upholds this mission," said Deborah Wiley, Chair of the Wiley Foundation. "We are pleased to highlight the impact that her research on messenger RNA decay pathways has had in advancing our knowledge of the cellular cause of many human diseases."

The department is pleased to announce the winners of the Sayeeda Zain Fall Travel awards: Debapratim Dutta, Sierra Fox and Hong Zhu.

The Sayeeda Zain Travel Award honors the distinguished career and charitable life of Dr. Sayeeda Zain. The award is given in recognition of research excellence to support travel and related expenses associated with attendance at a scientific conference or corporate internship to gain practical experience. The next round of Sayeeda Zain Travel Awards will be offered in Spring 2018.

Thank you to all those who applied and congratulations to Dave, Sierra and Hong!