Center for RNA Biomedicine

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From foundation to application: Alyssa English, Ph.D., Postdoctoral Fellow

One of the challenges of becoming an expert is to keep exploring broadly while being highly focused. Alyssa English, Ph.D., a postdoctoral fellow in Dr. Stephanie Moon’s lab, has found that by extensively studying basic science and rigorously applying the scientific method, she has acquired a strong foundation that allows her to tackle many different research areas. What she has learned from studying cellular processes in yeast will eventually serve her in disease research and keep the door open to many professional options. “My foundational training has prepared me very well to eventually pursue a career in industry,” she said.

In 2020, English joined the Moon lab to study the processes underlying severe neurological diseases. To answer fundamental biological questions, she now studies EIF2AK2, a gene that codes for protein kinase R (PKR), a major player in the integrated stress response which is a pathway that regulates transcription and translation in response to different stress signals such as pathogens. In particular, PKR responds to the presence of double-stranded RNA from viruses by inhibiting global translation. This prevents the cell from translating viral genes and, as a result, prevents further viral infection.

[Read more…] about From foundation to application: Alyssa English, Ph.D., Postdoctoral Fellow

 

On May 20th, 2021, the Board of Regents approved the following promotions of our RNA research community members:

  • Dawen Cai, associate professor of cell and developmental biology, with tenure, Medical School, and associate professor of biophysics, without tenure, College of LSA (featured scientist)
  • Justin A. Colacino, associate professor of environmental health sciences,  with tenure, and associate professor of nutritional sciences, without tenure, School of Public Health
  • Peter L. Freddolino, associate professor of biological chemistry, with tenure, and associate professor of computational medicine and bioinformatics, without tenure, Medical School (featured scientist and member of our Executive Committee)
  • Kenneth Kwan, associate professor of human genetics, with tenure, Medical School, and research associate professor in the Michigan Neuroscience Institute
  • Gustavo Mendonca, clinical professor, School of Dentistry
  • Melanie D. Ohi, professor of cell and developmental biology, with tenure, and research professor in the Life Sciences Institute (former member of our Executive Committee)
  • Sunitha Nagrath, professor of chemical engineering, with tenure, College of Engineering
  • Rajesh Rao, associate professor of ophthalmology and visual sciences, with tenure, and associate professor of pathology, without tenure, Medical School
  • Maureen Sartor, professor of computational medicine and bioinformatics, with tenure, Medical School, and professor of biostatistics, without tenure, School of Public Health
  • Anna A.S. Schwendeman, professor of pharmaceutical sciences, with tenure
  • Peter Todd, professor of neurology, with tenure, Medical School (featured scientist and member of our Executive Committee)

https://rna.umich.edu/8735-2/

In Memoriam, Charles R. Doering, Ph.D.

With great sadness we join the entire University of Michigan community in mourning Charles R. Doering, Ph.D., and expressing our deepest condolences to his colleagues, friends and loved ones.

Charles (Charlie) Doering was the Nicholas D. Kazarinoff Collegiate Professor of Complex Systems, Mathematics and Physics and was the Director of the Center for the Study of Complex Systems. He was a member of the U-M Center for RNA Biomedicine Strategic Advisory Board.

One of the great, polymath minds that found simplicity in complexity, Charlie generously shared his passion for modeling complex systems such as single-cell and multi-cellular organisms, and for deriving rigorous predictions. We are very grateful for his insightful participation in the Center’s leadership and for his support of the RNA research community.

“Charlie was always supportive of our efforts to envision and create our own Center, which in many ways was modeled after his successful, also LSA-based Center,” says Nils Walter, co-Director of the Center for RNA Biomedicine. “I owe him a personal thanks for his kind invitation and introduction to my presentation on the recent Nobel Prize in Chemistry for CRISPR-based genome editing, which allowed us to celebrate one of the many recent scientific breakthroughs that RNA research has given us.” [Read more…] about In Memoriam, Charles R. Doering, Ph.D.

U-M RNA scientists identify many genes involved in neuron development

Neurons result from a highly complex and unique series of cell divisions. For example, in fruit flies, the process starts with stem cells that divide into mother cells (progenitor cells), that then divide into precursor cells that eventually become neurons.

A team of the University of Michigan (U-M), spearheaded by Nigel Michki, a graduate student, and Associate Professor Dawen Cai in the department of Cell and Developmental Biology in the Medical School and in Biophysics in the College of LS&A, identified many genes that are important in fruit flies’ neuron development, and that had never been described before in that context.

 

Figure to the left: Neurons in the fruit fly brain are made by passing through various differentiation states, and are segregated into unique subtypes based on the age and cell division number of their mother cell (progenitor). The complexity of this process is modelled in the diagram above. Different RNAs play a role in these neuron formation steps. This study identifies many RNAs that were not previously known to be involved in these processes, and helps us better understand how this complex neuron-generation process works at the molecular level.

 

Since many genes are conserved across species such as between fruit flies (Drosophila), mice, and humans, what is learnt in flies can also serve as a model to better understand other species, including humans. “Now that we know which genes are involved in this form of neurogenesis in flies, we can look for them in other species and test for them. We work on a multitude of organisms at U-M and we’ve the potential to interrogate across organisms,” explains Michki. “In my opinion, the work we did is one of the many pieces that will inform other work that will inform disease,” adds Michki. “This is why we do foundational research like this one.”

Flies are also commonly used in many different types of research that might benefit from having a more comprehensive list of the fly genes with their associated roles in neuron cell development.

[Read more…] about U-M RNA scientists identify many genes involved in neuron development

The RNA Collaborative celebrates its first year of success!

Launched at the initiative of the University of Michigan Center for RNA Biomedicine, and inaugurated on April 22, 2020, with a seminar hosted by the Yale Center for RNA Science and Medicine, the RNA Collaborative Seminar Series is a growing grassroots effort, now supported by the international RNA Society and involving 21 RNA research partners from across the world, including the US and Canada, Asia, and Europe.

The RNA Collaborative aims to promote and disseminate the exciting RNA research currently emerging from across disciplines and academic institutions. It fosters and strengthens connections within the RNA scientific community across the globe. Within just one year, the Collaborative has welcomed 21 partners, demonstrating the dynamism of RNA research and the curiosity and collaborative spirit of RNA scientists.

“Congratulations to the RNA Collaborative in their milestone of uniting RNA researchers and advancing engaging and inclusive RNA science. The RNA Society is proud to be a partner in this incredible initiative and excited for the continued opportunity to work with the Collaborative to highlight the work of a diverse and highly talented group of researchers and spread their cutting-edge advances in RNA to our members and throughout the greater scientific community.”
—Kristian Baker, CEO, RNA Society

[Read more…] about The RNA Collaborative celebrates its first year of success!

RNA holds the reins in bacteria: U-M researchers observe RNA controlling protein synthesis

ANN ARBOR—To better understand how RNA in bacteria gives rise to protein—and along the way, target these processes in the design of new antibiotics—researchers are turning their attention to the unique way this process happens in bacteria.

In eukaryotic cells, transcription (the process by which information in a DNA strand is copied into messenger RNA) and translation (the process by which a protein is synthesized by the ribosome from the mRNA) are two successive steps. In bacteria, they occur simultaneously: As the RNA is being synthesized by RNA polymerase, the ribosome comes in to make the proteins.

This synchronicity allows for so-called “transcription-translation coupling,” wherein the first ribosome can immediately follow and couple with the transcribing RNA polymerase. It is a new area of research that promises to bring insights into processes unique to bacteria that could be targeted with great specificity in the design of antibiotics.

Now, University of Michigan researchers have directly observed previously hidden RNA regulatory mechanisms within such couplings. The results, spearheaded jointly by postdoctoral fellows Surajit Chatterjee and Adrien Chauvier of the U-M Department of Chemistry and the U-M Center for RNA Biomedicine, are published in the Proceedings of the National Academy of Sciences.

The new results promise to have important implications for the future design of antibiotics that could target the coupling mechanism instead of targeting the transcription or translation processes separately.

 

Caption: The 30S subunit of the ribosome can dynamically bind to the nascent mRNA as soon as its binding site emerges from the RNAP. Transcription factors and translation initiation factors assist in the initial binding and retention of the 30S subunit on the mRNA, resulting in the stabilization of an early initiation complex. During translation, the ribosome can follow the leading RNAP, establishing transcription-translation coupling and maintaining optimal transcription speed. In the presence of the ligand preQ1, transcription-translation coupling is disrupted, surprisingly leading to slow transcription.

[Read more…] about RNA holds the reins in bacteria: U-M researchers observe RNA controlling protein synthesis

Connecting neuronal activity to RNA and bench to bedside

A Ph.D. dissertation is a huge accomplishment, resulting from four, five or more years of intense research and training. To become a Ph.D. is a remarkable challenge both scientifically and intellectually that requires a deep personal and emotional commitment. A doctoral defense is not only the culmination of years of hard work, but it also raises the question of “what’s next for me?” after years on the schooling and training track.

On March 22, 2021, Ahmed Malik defended his Ph.D. thesis in Dr. Barmada’s lab, Department of Neurology, University of Michigan Medical School. For him, the “what’s next?” question finds answers in his passionate quest for knowledge and bioscience exploration. “There is so much to learn in school, and there is nothing else I’d rather be doing,” he said only a few days after defending his Ph.D.

 

“There is so much to learn in school, and there is nothing else I’d rather be doing.”

 

Malik is enrolled in the combined M.D.-Ph.D. program of the University of Michigan (U-M), one of the longest trainings offered at the university. When he joined U-M in 2014, he first did two years of classwork in the medical school as part of his M.D. training. Then he focused on the science behind neurodegenerative diseases and did his Ph.D. dissertation on an RNA-binding protein, Matrin-3, that plays a particular role in neurological diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). He is now getting ready to resume his M.D. training, while he is still debating between a specialization in neurology, psychiatry, or another clinical specialty. [Read more…] about Connecting neuronal activity to RNA and bench to bedside

From our 5th Annual Symposium: Advice to Trainees and Mentors

Top left to right: Markos Koutmos, Sara Aton, Chris Lima, and Kevin Weeks; bottom left to right: Feng Zhang, Tracy Johnson and Brenda Bass.

At the panel discussion of our 5th Annual Symposium held March 25–26, 2021, we asked the keynote speakers for advice for trainees and mentors. Brenda Bass from the University of Utah, Tracy Johnson from UCLA, Chris Lima from Sloan Kettering Institute, Kevin Weeks from University of North Carolina, and Feng Zhang from MIT drew from their personal experiences and shared best practices to become successful scientists. The discussion was led by University of Michigan faculty Sara Aton (Molecular, Cellular, and Developmental Biology) and Markos Koutmos (Chemistry and Biophysics), both members of the Center’s Executive Committee.

“Follow your passion” is a well-known recommendation, but it can take different meanings over time as you advance in your career. For example, a certain science might really speak to you and be really exciting, but you might find yourself alone on this path. In such a case, your passion might best be the leader. The advice is to take ownership of your path, and when it is not clear, trust that your passion will make things happen.

Passion is also contagious, and a mentor’s excitement transfers onto the mentees. A good connection between a mentor and a mentee is important in that a mentee needs a role model that they can admire so they accept advice from him or her. There is also a unique relationship between the mentor and each mentee. Each trainee has his/her own way of thinking, and it is the responsibility of the mentor to understand how his/her mentee processes information to best help the mentee. There is no formula across the board but leading by example, and staying empathetic, always applies.

[Read more…] about From our 5th Annual Symposium: Advice to Trainees and Mentors

Over 550 RNA fans attend our 5th Annual Symposium, March 25-26, 2021

With over 550 participants, this two-day symposium virtually gathered the vibrant RNA research community from the University of Michigan (U-M), the US, and around the world.

The symposium opened with remarks by Nils Walter, co-director of the U-M Center for RNA Biomedicine, who reminded the attendees of the importance of RNA research for society, as demonstrated by the COVID-19 RNA vaccine. Mats Ljungman, co-director of the U-M Center for RNA Biomedicine, emceed day 2.

Five distinguished keynote speakers presented on various RNA processes: Brenda Bass, Ph.D., University of Utah; Tracy Johnson, Ph.D., UCLA; Christopher Lima, Ph.D., Sloan Kettering Institute; Kevin Weeks, Ph.D., University of North Carolina; and Feng Zhang, Ph.D., MIT.

Six U-M junior and early career scientists presented their research in data blitzes: Adrien Chauvier, Ph.D., Postdoc and Research Assistant; Daniel Peltier, M.D., Ph.D., Clinical Lecturer; Meredith Purchal, Graduate Student; Cathy Smith, Graduate Student; Shannon Wright, Graduate Student; and Yan Zhang, Ph.D., Assistant Professor.

The panel discussion also provided many inspiring recommendations to trainees and mentors, from life/work balance and time management, to networking, and sharing scientific passion with one’s community. These will be summarized in the next issue of The RNA Transcript.

The Michigan Science Writers, a student organization dedicated to improving public understanding of science, graciously blogged about the event. READ THE BLOGS

The data blitzes were co-sponsored by Lexogen.
This event was supported by the University of Michigan Biosciences Initiative.

See the DETAILED PROGRAM.

Please respond to the symposium FEEDBACK SURVEY.

Together, we can do so much.
Thank you all for making this symposium such a success!

How the time was just right for developing a COVID-19 mRNA vaccine

Over 1,450 people attended our webinar with Melissa Moore, Chief Scientific Officer at Moderna Therapeutics, on March 3rd, 2021. In her presentation, Dr. Moore explained how the mRNA vaccine works, and how it was developed in record time of just 45 days. To put an end to this pandemic, she strongly encouraged the audience to get vaccinated, with any vaccine available, as soon as possible.

While we were all stunned by the rapid onslaught of the COVID-19 pandemic, the release of a clinically tested mRNA vaccine in less than a year was just as astounding, sounding almost too good to be true. Yet the speed at which this innovative way of making a vaccine became possible was based on years of cutting-edge RNA research that were ready to be taken to the next level.

[Read more…] about How the time was just right for developing a COVID-19 mRNA vaccine