Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt

Molecular Life of Stem Cells 2016 Conference of RNA Club Munich

Photo from the first day of MLSC2016 Conference, lecture of Paul Bertone (Cambridge University).

September 29 – October 1, 2016

Ljubljana, Slovenia

“I think the golden or even platinum age of both basic and applied research has begun. This is mainly due to plethora of recent transformative discoveries and technologies. These include advances in DNA sequencing, electron microscopy, gene-editing (correcting of genetic mutations) and the ability to convert regular cells to stem cells that could in the future be used for tissue repair. These advances currently accelerate basic research and will in time underpin novel strategies for regenerative medicine that could cure disease and slow ageing.” Donal O’Caroll, MRC Centre for Regenerative Medicine, The University of Edinburgh, UK.

The very first international conference “Molecular Life of Stem Cells 2016 (MLSC2016)” took place from September 29 to October 1, 2016, in Ljubljana, Slovenia. The main topics were as diverse as the speakers, ranging from stem cell biology, over RNA biochemistry to systems biology. The meeting was organized by Helmholtz Zentrum München in frame of the Munich RNA Club together with the University of Ljubljana and hosted by the City of Ljubljana. The event was organized free of any participation fee due to extensive support of all sponsors, in particular gold sponsors: Helmholtz Zentrum München, HELENA, ACD Bio, Lexogen, Eppendorf, Qiagene, Fluidigm and 10X Genomics.

One day before the main event pre-conference workshops were held, enabling students to benefit from more experienced colleagues and to discuss challenges young scientists are facing today. Courses on scientific writing, data mining, phyton programming, next generation sequencing and CRISPR/Cas9 genome engineering were held and later in the afternoon complemented by a series of introductory lectures about post-transcriptional regulation, epigenetics, RNA binding proteins, stem cells and translational research.

The conference started on September 29, 2016, with Jacob Hanna supported by EMBO Young investigator prize (Weizmann Institute of Science, Israel), who gave a notable overview about different human pluripotent stem cell cultures, which set the tone for many of the following talks (e.g. Paul Bertone, Cambridge University; Benjamin Dodsworth, Oxford University, and Jianlong Wang, Icahn School of Medicine at Mount Sinai, New York), resuming the discussion about naïve pluripotency in human and other primate species. Remarkably, research on rodent pluripotency concentrated especially on the loss of potency, as several talks (including an inspiring lecture from Jianlong Wang (Icahn School of Medicine at Mount Sinai, New York and talks from Martin Leeb (Max F. Perutz Laboratories, Vienna, Austria), Miha Modic (Helmholtz Zentrum München, Germany) and Joerg Betschinger (FMI, Basel, Switzerland) presented the molecular basis to exit pluripotency and somatic reprogramming that was in depth analyzed at single cell level (Davide Cacchiarelli, Harvard University, USA).

Many of the following sessions dealt one way or the other with the multiple functions RNAs can have in cells. While some speakers reported new classes of ncRNAs (Renee Schroeder, Max F. Perutz Laboratories, Vienna, Austria; Nikolaus Rajewsky, Max Delbruck Center, Berlin, Germany; Paolo Amaral, Gurdon Institute, Cambridge, UK) others presented new approaches to molecularly study the mechanism of well-known ncRNAs (e.g. Alena Shkumatava, Pasteur Institute, Paris, France) or new insights about their regulation in vivo in development (Jovica Ninkovich, HMGU and LMU, Germany) radiation response (Natasa Anasatov, Helmholtz Zentrum München, Germany) or in disease (Boris Rogelj, Institute Jozef Stefan, Slovenia).

The regulatory life cycle of RNAs was the main topic during the subsequent sessions (RNA regulatory networks, RNA structural regulatory principles, RNA-binding proteins (RBPs) in neurodegeneration and RNA regulation of neural differentiation). The protein binding mechanisms of RNAs, enabling functions or transport, were in the focus of several outstanding studies, including Dierk Niessing’s (Helmholtz Zentrum München, Germany) analysis of asymmetric RNA transport, Michael Sattler’s (TU Munich, Germany) structural analysis of RNA binding proteins and Jernej Murn’s report of the RNA binding protein Unkempt, which possesses the ability to transfer neuronal morphological features to non-neural cells. Especially noticeable among the many excellent talks were however two studies analyzing the degradation of RNAs in three different innovative ways, either during a directed process allowing oocyte maturation (Donal O’Caroll, MRC Centre for Regenerative Medicine, The University of Edinburgh, UK) or in a stochastic process only revealed by imaging of degradation speed in single somatic cells (Jeff Chao, FMI Basel, Switzerland) that can also be in unprecedented accuracy also computationally predicted (Julien Gagneur, TUM, Germany). Later, presentations focused on interplay between chromatin marks and splicing decisions (Christian Muchardt, Institute Curie, France), that is evolutionary modulated by the evolution of Alu elements underlying additional layer of complex splicing outcome (Jernej Ule, UCL and Crick Institute, UK) that can be visualized in real-time with recent advances in understanding transcriptional priming during T-cell activation (Elke Glasmacher, HMGU).

The meeting concluded with a short session on Epigenetics, starting with inspiring incorporation of unnatural amino acids with epigenetic marks in living cells (Simon Elsaesser Karolinska Institute) that can also be modified by further developing CRISPR/Cas9 methodology (Stefan Stricker, HMGU & LMU). Empowered with this revolutionary technique an excellent presentation revealed unexpected extent of DNA methylation turnover at CGI-islands bound by Polycomb complex that is both pluripotency stage- and Tet enzyme-specific (Sebastian Bultmann, LMU, Germany). Polycomb also facilitates regulatory activity of poised enhancers and thereby influence neuronal induction (Alvaro Rada-Iglesias, University of Cologne, Germany). We concluded the conference with proposition of Micha Drukker (Helmholtz Zentrum München, Germany) to use iPSC technology for the sake of species conservation and an active discussion on presented themes. The support of RNA Society and Stem Cell Technologies enabled two poster awards, which went to; Elena Galimberti from University of Vienna and Markus Grosch from Helmholtz Zentrum München and support of Boehringer Ingelheim Stiftung enabled participation of 2 outstanding junior scientists.

The conference “Molecular Life of Stem Cells 2016” was planned with the subtitle “post-transcriptional regulation and (epi-)genomic engineering in stem cells” in mind. Despite this already rather loose underlying theme, an excellent group of speakers managed repeatedly to penetrate areas not necessary expected from an ordinary stem cell conference. Amongst the most impressive talks reporting new insights or technological advances were even quite some not relying on stem cells at all. Especially those, reporting on the multiple roles RNA molecules can play, were often conducted in established cell lines, yeast or even bacterial cultures (Renee Schroeder, University of Vienna). Essential role in progression of understanding molecular mechanisms carry also leading research companies that presented advances in single cell analysis (10X Genomics, Advanced Cell Diagnostics, Fluidigm) and sequencing methodologies (Lexogen GmbH, Qiagene). Therefore, the meeting could have easily bared a title even less defined than the chosen one; why did the conference then feel so coherent? There is likely a single answer to this: After decades differentiating branches of molecular biology, in which scientific phenomena were sometimes studied for their own sake, there is a multidisciplinary movement noticeable today, aiming to identify the functionally relevant mechanisms from the myriad of molecular processes described. As a direct consequence, a new curiosity of researchers towards related, but mechanistically diverse topics sets the ground for hopefully a large number of such multifaceted meetings in the near future.

Miha Modic, Tjasa Lepko and Stefan H. Stricker