Center for RNA Biomedicine

Ann Arbor, MI

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First step first: understanding normal processes before tackling pathologies

Photo: Adrien Chauvier, Ph.D., in the Nils Walter’s lab (Credit: Laura Penabad-Peña)

 

Dr. Adrien Chauvier’s journey has taken him around the world, from the Amazon rainforest to Michigan snowy winters, and his passion for science has never left him. He is now a postdoctoral fellow in Nils Walter’s lab, in the Department of Chemistry of the University of Michigan.

Dr. Chauvier grew up in the equatorial forests of French Guiana, north of Brazil. French Guiana is an important biodiversity hotspot and is also the largest French territory outside the metropole.

His father owned a large plant nursery and he is the one who instilled a deep interest for the natural world into him. ” I always wanted to go outside with my dad. I was very curious. We would take care of the plants and the soil together. It was no surprise that growing-up, I wanted to pursue a career in Science and especially in the biological field (…),” he fondly recalled. [Read more…] about First step first: understanding normal processes before tackling pathologies

How sleep loss sabotages new memory storage in the hippocampus

While some students may think it’s a good idea to pull an all-nighter before an exam, conventional wisdom may be correct: a good night’s sleep may actually be more helpful, according to University of Michigan research.

U-M scientists Sara Aton and James Delorme found when mice are sleep deprived, there is an increase in activity in inhibitory neurons in the hippocampus, an area of the brain essential for navigation, as well as for processing and storing new memories.

“Because these neurons limit activity in their neighbors, this physiological response makes it impossible to muster normal neuronal activity in the hippocampal structure,” said Sara Aton, an associate professor in the U-M Department of Molecular, Cellular and Developmental Biology and a member of the U-M Center for RNA Biomedicine executive committee. “I always tell my students that an overnighter is not helping them prepare for an exam.”

The researchers’ results are published in the Proceedings of the National Academy of Sciences, and their findings could have implications for human performance and learning strategies.

 

Image: Somatostatin-expressing interneurons in the mouse dentate gyrus, labeled with Brainbow 3.0 (which labels each neuron a distinct color). cFos (labeled green) is present in the nuclei of surrounding pyramidal cells which are active during sleep. Image by Frank Raven

[Read more…] about How sleep loss sabotages new memory storage in the hippocampus

An often overlooked cause of genetic disease

by Elisabeth Paymal

Often overlooked because they might not alter the amino acid production, splicing defects can play an important role in rare genetic pituitary gland diseases.

Several clinical endocrinologists and bioinformaticians, led by Sally Camper and Jacob Kitzman, Professors of Human Genetics at the University of Michigan Medical School (UMMS), came together to further investigate splicing defects and their roles in rare genetic hormonal diseases. Cathy Smith, a PhD student, established a catalog of predicted variants that could either be tolerated or disease causing.

The pituitary gland is a very important center for hormonal activity. It produces several different hormones which control growth and the functions of other endocrine glands. Specific to the pituitary gland is POU1F1 (also known as PIT1), a transcription factor critical for the development of three of the hormone-producing cell types: growth hormone, prolactin, and thyroid stimulating hormone. Most of the time, a mutation in POU1F1 is recessive, but there are some cases when the variants have a dominant effect. Either genetic cause usually results in multiple hormone deficiencies.

Figures: POU1F1 acts as a dimer and binds to its own gene and the growth hormone to activate transcription (figure 1). The patient variants shift splicing to producing the repressor isoform, which can block the action of the alpha isoform produced from the normal gene copy of POU1F1 (figure 2). This results in less POU1F1 transcription, fewer hormone producing cells, and less growth hormone.

[Read more…] about An often overlooked cause of genetic disease

A call for direct sequencing of full-length RNAs to identify all modification

For most organisms, DNA sequences are available, but the complete RNA sequences are not. Here, we call for technologies to sequence full-length RNAs with all their modifications. Article co-authored by Dr. Vivian Cheung, member of our Center.
Publication: Alfonzo, J.D., Brown, J.A., Byers, P.H. et al. A call for direct sequencing of full-length RNAs to identify all modifications. Nat Genet (2021). https://doi.org/10.1038/s41588-021-00903-1

Building a better scientific world with hands-on science

Sometimes it takes exploration outside our usual interests to find our true passion. This is what happened to Sydney Rosenblum, now a graduate student in Rackham Graduate School Program in Chemical Biology, in Professor Amanda Garner’s lab. In high school, Sydney felt that “science was not for her,” somewhat irrelevant or too abstract, until she serendipitously took a biotechnology class offered through a special program sponsored by the State of California. Obscure science became hands-on, and she was hooked. “It was really cool to actually be able to manipulate biology in the lab,” she fondly recalls. “It was also very exciting to learn about new pivotal discoveries, like DNA sequencing, things that you usually learn about only until much later.”

This advanced class offered a mix of foundational theory and lab experience with an internship in a small biotech company focused on plant genetics. After this first exposure to science research and discovering like-minded people, Sydney had no doubt about what she wanted to do. She went on to get an undergraduate degree in biochemistry, with the understanding that she would pursue graduate studies and a doctorate that would eventually allow her to join a biotech company.

Now in Professor Garner’s lab, Sydney is developing a cellular platform to study RNA-protein interactions that play a role in cancerous tumor growth. Lin 28 is an RNA binding protein that can inhibit a family of microRNAs, let-7, which blocks the expression of certain genes that promote cancerous growth. Over the next few months, Sydney will be screening for small molecules that could block this RNA-protein interaction, with the goal of restoring normal processing of let-7 microRNAs and its tumor suppressor activity.[1]

Photo: Sydney Rosenblum cultures mammalian cells in the laminar flow hood. Credit: Sara Khan

[Read more…] about Building a better scientific world with hands-on science

To splice or not to splice…

by Elisabeth Paymal

In an article published in the journal RNA [1] , Karan Bedi, a bioinformatician in Mats Ljungman’s lab, Department of Radiation Oncology at the University of Michigan Medical School, investigated the efficiency of splicing across different human cell types. The results were surprising in that the splicing process appears to be quite inefficient, leaving most intronic sequences untouched as the transcripts are being synthesized. The study also reports variable patterns between the different introns within a gene and across cell lines, and it further highlights the complexity of how newly transcripts are processed into mature mRNAs.

Several processes take place to produce mature mRNAs that then can be exported to the cytoplasm and used as a template for protein synthesis. After initiation of transcription and the go-ahead of elongation to produce the pre-mRNA, introns need to be spliced out and the protein-coding exons connected.   At first, pre-mRNA is made as a complementary sequence of the DNA but with slightly different chemistry and includes all the introns. Then the spliceosome machinery, made up of about 300 proteins, assembles “co-transcriptionally” at each intron junction as the RNA emerges from its synthesis. “Splicing is an incredibly complex process because of the great number of proteins involved that repeatedly need to assemble and disassemble at each junction. Also, the speed at which transcription generates RNA is quite fast so the splicing process has to be well organized. Many steps can go wrong and lead to various pathologies, which is why it is so important to have a better understanding of how splicing happens and how it is regulated,” said Bedi.

Photo: Karan Bedi explains the complex data analysis pipeline. Professor Ljungman is on the left – credit: Elisabeth Paymal

[Read more…] about To splice or not to splice…

A warm thank you to LSA Technology Services!

As we are hosting our last seminar of the academic year with the RNA Collaborative Seminar Series this Wednesday, June 30th, we want to give special thanks to the infallible support we have received from LSA Technology Services.

Like all of us, we were quite baffled by the pandemic social distancing and the necessity to quickly implement virtual events. The LSA Technology Services team, especially Chris Taylor, Rob Feeley and Keith Kuras, has proven invaluable to educate us on the best tools and tips to run successful virtual events. “Live events can be stressful, and it was such a relief to know that they were with us every step of the way. They fixed issues before I even noticed them, I almost felt like they were our guardian angels!” said Martina Jerant, Center for RNA Biomedicine Manager.

All along, the LSA Technology Services team has been very dedicated to the success of our events and, since March 2020, has offered 40 tests/consultations and has accompanied 22 of our events. “Being a part of the RNA Seminars has been a wonderful experience and a series I look forward to supporting. Martina, department faculty and staff as well as the guest speakers are always gracious, and working with them is always a pleasure,” kindly said Chris Taylor.

We are very grateful for their generosity and efficiency, and we look forward to working together again!

The Pandemic Academic Year

As we end the 2020–21 academic year, we’re still pondering the impact of RNA research on the pandemic that is changing the world we live in. As RNA scientists, we applaud the mRNA vaccine development and how scientists pivoted their research to contribute to SARS-CoV-2 and COVID-19 research. These extraordinary scientific achievements and the pandemic are also revealing deep social justice issues, and we are thrilled by the recent announcement that a billion doses of COVID-19 mRNA vaccines will be made available to the world for free. Together, the RNA scientific community is saving millions of lives.

Closer to home, this year has also been an unexpected opportunity to further strengthen our local, national, and international outreach. We offered 17 one-hour Zoom webinars, our RNA Innovation Seminar Series, where RNA scientists presented their latest work on a broad range of topics, from foundational biology to potential therapeutics. These seminars fostered new insights and synergies for potential collaborations. Our members were given the opportunity to meet individually with these presenters and explore possible partnerships. [Read more…] about The Pandemic Academic Year

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/