Craig Mello, Ph. D.
Professor, UMass Medical School, USA
Nobel Prize in Physiology or Medicine (2006)
Dr. Mello’s lab uses the nematode C. elegans as a model system to study embryogenesis and gene silencing. His collaborative work with Dr. Andrew Fire led to the discovery of RNA interference (RNAi), for which they shared the 2006 Nobel Prize in Physiology or Medicine. Together they showed that when C. elegans is exposed to double-stranded ribonucleic acid (dsRNA), a molecule that mimics a signature of viral infection, the worm mounts a sequence-specific silencing reaction that interferes with the expression of cognate cellular RNAs. Using readily produced short synthetic dsRNAs, researchers can now silence any gene inorganisms as diverse as rice and humans. RNAi allows researchers to rapidly “knock out” the expression of specific genes and, thus, to define thebiological functions of those genes. RNAi also provides a potential therapeutic avenue to silence genes that cause or contribute to diseases.Dr. Mello received his BS degree in Biochemistry from Brown University in 1982, and PhD from Harvard University in 1990. From 1990 to 1994, he conducted postdoctoral research at the Fred Hutchinson Cancer Research Center in Seattle, WA. Now Dr. Mello is an Investigator of the Howard Hughes Medical Institute, the Blais University Chair in Molecular Medicine and Co-director of the RNA Therapeutics Institute at the University of Massachusetts Medical School.Besides the Nobel Prize, Dr. Mello’s work was recognized with numerous awards and honors, including the National Academy of Sciences Molecular Biology Award (2003), the Wiley Prize in Biomedical Sciences from Rockefeller University (2003), Brandeis University’s Lewis S. Rosnstiel Award for Distinguished Work in Medical Research (2005), the Gairdner Foundation International Award (2005), the Massry Prize (2005), the Paul Ehrlich and Ludwig Darmstaedter Award (2006), the Dr. Paul Janssen Award for Biomedical Research (2006), the Hope Funds Award of Excellence in Basic Research (2008). He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society.
Tsutomu Suzuki, Ph. D.
Professor, Department of Chemistry and Biotechnology, Graduate School of Engineering, the University of Tokyo, Japan
Tsutomu SUZUKI obtained his Ph.D. in Tokyo Institute of Technology in 1996, took a job in a pharmaceutical company, and started his career as an RNA biochemist in University of Tokyo in 1997. In 2004, he became independent and started his lab focusing on RNA modification and protein synthesis. Professor SUZUKI’s lab has developed a platform technology for isolating individual RNAs, and analyzing their modifications by mass spectrometry. So far, they discovered several novel modifications and dozens of RNA-modifying enzymes. His group also reported the first instance of human disease caused by RNA modification deficiency. Last year, Professor SUZUKI started a JST ERATO project on RNA modification as a director for 6 years. Further information about his lab and their research can be found at
RNA Modifications in Health and Disease
RNA molecules are frequently modified post-transcriptionally, and these modifications are required for proper RNA functions. To date, about 150 different types of chemical modifications have been identified in various RNA molecules across all domains of life. There are still a number of novel modifications to be discovered. RNA modifications appear to confer chemical diversities to simple RNA molecules basically composed of four letters, to acquire a greater variety of biological functions. These modifications play critical roles in stability and functions of RNA molecules. We’ve been carrying out a project to identify novel RNA modifications from various sources, and reported seven modifications so far. Taking advantage of mass spectrometric analysis of RNA modifications, we systematically screened a series of knockout strains for uncharacterized genes, and identified more than 40 genes responsible for tRNA modifications, rRNA modifications as well as mRNA modification. We identified a cap-specific adenosine methyltransferase (CAPAM) responsible for N6-methylation of m6Am at the transcription start site of eukaryotic mRNAs, and have been studying a role of this modification in protein synthesis. Recently, we revealed function of m6A in U6 snRNA in efficient splicing of pre-mRNAs.
It has been generally thought that tRNA modifications are stable and static, and their frequencies are rarely regulated. We previously reported that lack of tRNA modification causes major classes of mitochondrial diseases including MELAS and MERRF. Deficient tRNA modification results in defective protein synthesis, leading to mitochondrial dysfunction. These findings provided the first evidence of human disease caused by an RNA modification disorder. We call “RNA modopathy” as a new category of human diseases. I am going to show our recent studies on RNA modifications associated with human diseases and their dynamic regulation by sensing intracellular metabolites under physiological condition.
Joachim Lingner, Ph. D.
Professor, Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
Joachim Lingner obtained his PhD (1992) at the Biozentrum of the University of Basel in the laboratory of Walter Keller studying the 3’ end formation of messenger RNAs. During his postdoctoral work (1993-1997) with Thomas Cech at the Howard Hughes Medical Institute of the University of Colorado at Boulder, Lingner discovered the catalytic subunit of telomerase (TERT) which counteracts telomere shortening and cellular senescence in cancer cells, stem cells and the germ line. Since 1997, Lingner is group leader at ISREC and since 2005 professor at the EPFL in Lausanne, Switzerland. The Lingner lab studies how telomeres enable chromosome stability and how they are maintained to regulate cellular lifespan. The team elucidated how the telomerase enzyme is regulated at chromosome ends to counteract telomere shortening. The lab also discovered that telomeres are transcribed into long the long noncoding RNA TERRA, which regulates telomeric chromatin structure and telomere maintenance by telomerase and homology directed repair. Finally, his team developed techniques to purify telomeric chromatin and determine its protein composition by mass spectrometry to uncover the changes that occur in the telomeric proteome during aging and disease including cancer. Lingner obtained a START-fellowship from the Swiss National Science Foundation (1997), the Friedrich Miescher prize (2002), an ERC advanced investigator award (2008) and is an elected member of EMBO (2005) and the Academia Europaea (2020).
Regulation of Telomere Maintenance by the Telomeric Long Noncoding RNA TERRA
Telomeres correspond to the physical ends of eukaryotic chromosomes. They protect chromosome ends from DNA degradation and rearrangements. Telomeres also serve as cellular clocks. Due to the end replication problem, they shorten with every round of DNA replication limiting the lifespan of most human somatic cells. Telomere shortening is overcome in stem cells and in cancer by the telomerase enzyme. In addition, telomere shortening can be counteracted by homologous recombination engaging telomeric DNA of different chromosome ends. Telomeres are associated with a large number of proteins which mediate telomere functions. The telomeric long noncoding RNA TERRA, which is transcribed at chromosome ends is another important telomeric component. Its roles have just started to be unraveled. Among others, TERRA has been implicated in modulating DNA damage signaling and telomere maintenance by homology directed repair when telomeres are damaged or very short. Our data demonstrate that TERRA association with telomeres involves formation of DNA:RNA hybrid structures known as R-loops whose formation can be triggered post transcription by the RAD51 DNA recombinase. TERRA preferentially associates with short telomeres where TERRA R-loops can stimulate homologous recombination between telomeric repeats of different chromosome ends to promote telomere elongation. On the other hand, TERRA R-loops can also interfere with telomere maintenance when present in S phase as they clash with the semiconservative DNA replication machinery. To prevent this, several telomeric proteins counteract TERRA R-loops. In this talk, I will report on the identification of factors that regulate TERRA association and R-loop formation at chromosome ends and how this impinges on telomere maintenance by DNA replication and homology directed repair.
David Bartel, Ph.D.
Professor, Whitehead Institute for Biomedical Research and Investigator of the Howard Hughes Medical Institute
David Bartel received his Ph.D. from Harvard in 1993 and soon thereafter began heading a lab at the Whitehead Institute for Biomedical Research, where he is also an Investigator of the Howard Hughes Medical Institute and a Professor of Biology at MIT. His lab initially studied the ability of RNA to catalyze reactions and more recently has focused on RNAs that regulate gene expression. Over the past 20 years his lab has helped define microRNAs and other types of small regulatory RNAs and has contributed to the understanding of their genomics, biogenesis and regulatory targets, as well as the molecular and biological consequences of their actions in animals, plants and fungi.
Regulation of mRNA Translation and Decay
Our lab investigates the molecular pathways that regulate gene expression by affecting the stability or translation of mRNAs. One interest is microRNAs, which are small regulatory RNAs that typically direct the destruction of their target transcripts. For example, we have recently discovered the mechanism by which some unusual target transcripts direct the destruction of microRNAs, and the widespread use of this phenomenon to shape metazoan microRNA levels. MicroRNAs cause more rapid shortening of the poly(A) tails of their mRNA targets. In most contexts, tail shortening reduces mRNA stability, but in early development, it reduces mRNA translation. We have recently gained new insight into the molecular basis of this developmental switch in posttranscriptional gene-regulatory regimes, explaining why in oocytes and early embryos tail shortening reduces mRNA translation but not mRNA stability, whereas later in development tail shortening reduces mRNA stability but not translational efficiency.
Ravindra K Gupta, Ph.D.
Professor of Clinical Microbiology, Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Jeffrey Cheah Biomedical Centre, University of Cambridge
Ravi Gupta has been Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases since 2019. Having completed his medical undergraduate studies at Cambridge and Oxford Universities, he pursued a Masters in Public Health at Harvard as a Fulbright scholar. Upon return he trained in infectious diseases in Oxford and London (UCLH, Hospital for Tropical Diseases) and completed his PhD at UCL on lentiviral evasion of antiretrovirals and innate immune responses. He has worked extensively in HIV drug resistance, both at molecular and population levels, and his work demonstrating escalating global resistance led to change in WHO treatment guidelines for HIV. Whilst Professor at UCL, he led the team demonstrating HIV cure in the ‘London Patient’ – the world’s only living HIV cure, and the second recorded in history (Gupta et al, Nature 2019). In 2020 he was named as one of the 100 Most influential people worldwide by TIME Magazine. He has deployed his expertise in RNA virus genetics and biology during the COVID-19 pandemic to report the first genotypic-phenotypic evidence for immune escape of SARS-CoV-2 within an individual, defining the process by which new variants likely arise (Kemp et al, Nature 2021), and also reporting some of the first data on Pfizer BioNTech vaccine-induced antibody responses against the B.1.1.7 variant that arose in the UK (Collier, De Marco et al, Nature 2021). In addition his group has defined poorer vaccine responses in the elderly, particularly with regard to variants of concern (Collier, Ferreira et al, Nature 2021). Most recently Gupta’s work has defined the immune escape and transmissibility advantage of the Delta variant as the drive behind global expansion of this variant.
SARS-CoV-2 Variants and Implications for Vaccines
SARS-CoV-2 has continued to surprise the world in its ability to generate diversity and evade vaccine induced immune responses, specifically neutralising antibodies. Chronic infection with SARS-CoV-2 was recognised in 2020 but us and others, with mutant viruses detected with multiple mutations in both spike and across the genome. In this talk I will outline how new variants have arisen and the key features of the variants of concern. The talk will highlight some of the mechanistic differences in their biology with reference to specific mutations, and what this means for transmission and vaccine efficacy. The data from clinical trials and correlate of protection studies will be reviewed and future directions for vaccines discussed.
Biliang Zhang, Ph. D.
President, Guangzhou RiboBio Co., Ltd
Biliang Zhang received his M.S. in Organic Chemistry from Fordham University in 1990, Ph.D. in Organic Chemistry with Prof. Ronald Breslow at Columbia University in 1995, and conducted his post-doctoral training with Prof. Thomas Cech at University of Colorado Boulder. In 1998 Dr. Zhang became an Assistant Professor of the Program in Molecular Medicine at University of Massachusetts Medical School. In 2004 he accepted a Principal Investigator role at the Guangzhou Institute of Biomedicine and Health of Chinese Academy of Sciences, where he currently holds a Professor position. Using diverse biological and chemical methodologies, Dr. Zhang’ s lab studies the roles of RNA molecules in living cells. His particular interests are in the fields of non-coding RNAs, nucleic acid synthetic biology and therapeutics. In 2004, Dr. Zhang established Guangzhou RiboBio Co., Ltd.