Summary:
For decades that central dogma stated that information flowed from DNA to proteins via translation. In this process RNA was consisdered to be a passive participant simply shuttling the genetic code from the chromosome to the ribosome. However, emerging studies have discovered a great number of biological processes in which RNA plays an active regulatory role. For example, so-called micro-RNAs which are typically only 22 bases and do not code for a protein, have been shown to directly influence gene expression by ‘silencing’ target mRNAs. At another level, RNA can be chemically modified post-transcriptionally. This process, called epitranscriptomics in analogy to post-translational modification of protein and DNA known as epigenetics, alters the functional behaviour of modified RNAs. In the last 5 years, work from the laboratories of the two speakers has begun to elucidate the role and mechanism of transformation of a healthy cell to a diseased one when specific RNA modifications become misregulated.

Based upon the insights of our two speakers, amongst others, numerous companies have been launched whose goal is to develop small molecule inhibitors of misregulated epigenetic processes. Biotechs such as Storm Therapeutics, 28-7, Gotham Therapeutics and Accent Therapeutics amongst many others, are all making headlines in this space…and big pharma has taken notice. Targeting both RNA and the proteins that interact with it has become one of the hottest new areas in drug discovery. Here we will bring you two key opinion leaders who will share their insights into the mechanisms of epitranscriptomics and its relationship to disease, in particular oncology. They will describe their latest findings on important targets and the biological outcome of inhibiting them. In addition, ZoBio will share a case study on development of small molecule inhibitors of an epitranscriptomic target. In all, the webinar will bring you insights into the field, the propsects for drug discovery and what it takes to be successful if you chose to pursue it.

Professor Samie Jaffrey’s lab has focused on the role of m6A methylation in translation of mRNA. His lab has developed technology to map this modification in the cellular transcriptome and defined many of the so-called writers, readers and erasers in the process. Here he will discuss the YTHDF family of readers that selectively recognize m6A mRNA and their role in leukemia and describe requirements for effective small molecule intervention.

Professor Sebastian Leidel’s lab investigates the role of tRNA modifcation and how this effects translation. In his talk he will discuss recent results from his laboratory that demonstrate how the loss of specific modfications can result in the disease state, in this case with severe neurological consequences.

Speakers:

Prof. Sebastian Leidel
Professor for RNA Biochemistry, Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) University of Bern, Switzerland

Sebastian Leidel has been a Full Professor for RNA Biochemistry in the Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) of the University of Bern (Switzerland) since 2018. Prior to this, he led an independent research group at the Max Planck Institute for Molecular Biomedicine in Münster (Germany). He has worked in the field of chemical modification of RNA for more than 15 years. The key question his research focuses on is how naturally occurring RNA modifications mediate cellular functions and how their absence triggers disease.

Prof. Samie R. Jaffrey, M.D., Ph.D.
Greenberg-Starr Professor of Pharmacology, The Department of Pharmacology at the Weill Cornell Medicine, New York, NY

Dr. Samie R. Jaffrey is the Greenberg-Starr Professor in the Department of Pharmacology at the Weill Cornell Medical College. Dr. Jaffrey’s work has fundamentally advanced our understanding of RNA biology and gene regulation. Most recently, he helped to launch the field of “epitranscriptomics,” which has revealed that mRNA and long noncoding RNAs are regulated by nucleotide modifications that impact their fate and function in cells. Dr. Jaffrey’s transcriptome-wide mapping of N6-methyladenosine (m6A) in 2012 revealed that m6A is a pervasive modification in the transcriptome, thereby identifying this modification as a fundamentally novel form post-transcriptional mRNA regulation. Since this seminal study, Dr. Jaffrey mapped dimethyladenosine (m6Am) and established functions of m6A and m6Am as well as m6A and m6Am reader, writer, and eraser proteins. The mapping methods developed by Dr. Jaffrey has been the essential tool in epitranscriptomics, and has transformed our understanding of gene regulation in normal and disease states. Dr. Jaffrey’s is an elected member of the American Society for Clinical Investigation, and the recipient of the 2017 John J. Abel Award in Pharmacology, the 2014 American Society for Biochemistry and Molecular Biology, the Young Investigator Award Klingenstein Neuroscience Award, Irma T. Hirschl Scholar Award, the McKnight Foundation Technology Development Award, NIH EUREKA Award, the NIH Director’s Transformative R01 Award, and the 2013 Blavatnik Award for Young Scientists.

Moderator:

Dr. Gregg Siegal
CEO, ZoBio