Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
"Microtubules are dynamic cytoskeletal filaments that control different aspects of cell architecture. Microtubules are intrinsically asymmetric polymers, with fast-growing plus ends, which in cells serve as major sites of microtubule assembly and disassembly, and slow-growing minus ends, which are often stabilized and attached to different cellular structures. In my lab, we use in vitro assays combined with single molecule imaging to dissect how the proteins that bind to microtubule plus- and minus ends control microtubule nucleation and dynamics. In parallel, we employ live cell imaging to study how microtubules contribute to cell polarity, migration, division and differentiation. The combination of in vitro reconstitution assays with experiments in cells allows us to decipher how the specific molecular properties of microtubule regulators contribute to cellular function and how microtubule-targeting anti-cancer drugs affect the cytoskeleton."
Anna Akhmanova studied biochemistry and molecular biology at the Moscow State University. She received her PhD in 1997 at the University of Nijmegen, the Netherlands. In 2001, she has started her own research group at the Department of Cell Biology at the Erasmus Medical Center, Rotterdam, the Netherlands. Since 2011, Anna Akhmanova is professor of Cell Biology at Utrecht University, the Netherlands. Akhmanova studies cytoskeletal organization and trafficking processes, which contribute to cell polarization, differentiation, vertebrate development and human disease. She is an expert on microtubule dynamics and microtubule-based membrane trafficking. Akhmanova is a recipient of the Netherlands Organization for Scientific Research (NWO) Spinoza Prize (2018), the highest scientific distinction in the Netherlands. She is an elected member of the European Molecular Biology Organization (EMBO) and the Royal Netherlands Academy of Arts and Sciences (KNAW). Akhmanova serves as a Deputy Editor of eLife, an Open Access journal in Life Sciences.
Cell Biology, Medical Research Council - Laboratory for Molecular Cell Biology (MRC-LMB), University College London (UCL), London, United Kingdom
"In this talk, I will explore what we can learn about the fundamentals of cell division and its evolution by studying the process in both archaea and eukaryotes."
Following his first degree in Biochemistry at the University of Oxford, Buzz obtained his PhD studying the cell division cycle with Paul Nurse at CRUK's London Research Institute. Buzz then explored cell shape in Drosophila as a postdoctoral researcher with Norbert Perrimon at Harvard Medical School. Since then, Buzz has led his own group studying cell shape changes through the cell cycle at UCL’s Ludwig Institute for Cancer Research, at UCL’s MRC LMCB, and as a satellite group leader at the Francis Crick Institute. Then in 2020, Buzz joined the MRC-LMB in Cambridge. There, having long studied cell division in eukaryotes, the realisation that many of the core machines involved in cell division have been conserved over billions of years has led his team to begin studying cell division in our archaeal relatives. By doing so, his team aims to put the ‘inside-out model of eukaryogenesis” to the test and to get at the fundamental molecular and cellular processes that underpin eukaryotic cell biology.
Department of Chemical and Structural Biology, Weizmann Institute of Science, Rechovot, Israel
"Dr. Diskin investigates how different proteins interact and form complexes and how such interactions underlie various pathological conditions, such as viral infections. In addition, the Diskin lab studies molecular mechanisms of anti-viral immune responses and develops novel immunotherapeutic approaches."
Dr. Ron Diskin was born and raised in Jerusalem. He received his B.Sc. in life sciences in 2003 and his M.Sc. in biochemistry in 2004, both magna cum laude from the Hebrew University of Jerusalem, where he also obtained his Ph.D. in 2008, studying signaling pathways using X-ray crystallography. After completing postdoctoral training at the California Institute of Technology, Dr. Diskin joined the faculty of chemistry at the Weizmann Institute of Science as an assistant professor in 2012 and became an associate professor in 2020.
Laboratory of Cell Architecture, Helmholtz Zentrum München, München, Germany
"Cells accomplish the biochemical reactions of life by concentrating their proteins into a variety of subcellular compartments called organelles. Our group explores the relationship between the form of the organelle and the function of its resident macromolecules. How does organelle architecture direct molecular function, and reciprocally, how do macromolecules sculpt and shape organelles? To investigate these questions, we use focused ion beam (FIB) milling of frozen cells followed by cryo-electron tomography to image macromolecules within their native cellular environment. Through a combination of nanometer-precision localization and high-resolution structural analysis, we aim to chart the molecular landscapes of organelles. Thanks to its superb cryo-EM contrast and textbook organelle architecture, the unicellular green alga Chlamydomonas is an ideal specimen for this technique. We have extensively explored these algae, with in situ molecular studies of the nuclear envelope, ER, Golgi, basal body apparatus (centrioles), and chloroplast. In this talk, I will provide an overview of some of these studies, touching on proteasome-rich degradation centers (Albert et al., 2017; 2020), the nuclear pore complex (Mosalaganti et al., 2018), and the molecular organization of chloroplast’s thylakoid membranes (Wietrzynski et al., 2020; Gupta et al., 2021) and liquid-like pyrenoid (Freeman Rosenzweig et al., 2017; He et al., 2020)."
Ben Engel received his bachelor’s degree from the University of California, Berkeley and performed his Ph.D. studies with Wallace Marshall at the University of California, San Francisco. After spending the first three decades of his life in the Bay Area, he said goodbye to USA, and has lived in Munich, Germany ever since. He was a postdoc and project group leader in the department of Wolfgang Baumeister at the Max Planck Institute of Biochemistry. In 2019, he started an independent research group at the Helmholtz Pioneer Campus at Helmholtz Zentrum München. Dr. Engel is a member of the EMBO Young Investigator Program.
School of Medicine, University of Colorado, Denver, USA
"Biomedical research disciplines are awash in data. These data, generated by new technologies as well as old approaches, provide the opportunity to systematically extract biological patterns that were previously difficult to observe. I’ll share vignettes focusing on three areas: 1) why large-scale integrative analyses can be beneficial in bioinformatics; 2) how data simulation can help us avoid rediscovering generic findings; and 3) how machine learning can be used to examine the scientists whose contributions we choose to recognize."
Casey’s lab at the University of Colorado School of Medicine is dedicated to developing computational tools that biologists can use to gain insights from other labs’ data as easily as from their own. The lab’s work is heavily motivated by the interests of its members, and in recent years the lab has also examined the distribution of honors by a major computational biology society, investigated preprints as a means to study the peer review process, and developed methods to promote data sharing. In 2016, Casey established the “Research Parasite Awards” after an editorial in the New England Journal of Medicine deemed scientists who analyze other scientists’ data “research parasites.” These honors, accompanied by a cash prize, are awarded to scientists who rigorously reanalyze other people’s data to learn something new. Casey is also the director of the Center for Health AI at the University of Colorado School of Medicine. This newly created center will be made up of faculty dedicated to enhancing research, clinical practice, and education with the use of advanced analytical approaches. Initial recruits to campus made through the center include Sean Davis and Melissa Haendel.
Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden
Thomas Helleday is Swedish and obtained PhD in 1999 from Stockholm University on his studies on homologous recombination in mammalian cells. After a short post-doctoral research period with Mark Meuth at the Institute for Cancer Studies, University of Sheffield, UK, he obtained a lectureship in 2000 at the same institute and set up his own group. Dr Helleday became professor at both University of Sheffield and Stockholm University in 2006, prior to being recruited as MRC Professor of Cancer Therapeutics at the MRC/CRUK Gray Institute for Radiation Oncology and Biology at the University of Oxford. In 2012, he was called to the Torsten and Ragnar Söderberg Professor of Translational Medicine and Chemical Biology at Science for Life Laboratory at the Karolinska Institutet in Stockholm, heading a division for translational medicine. In 2018 he returned to University of Sheffield to establish the Sheffield Cancer Centre, a joint initiative between the NHS and the University. Following the corona pandemic, he returned to Karolinska Institutet in 2020 to focus on translational research in his group. The focus of the research in the Helleday lab has been translational medicine in the DNA damage response and repair area, exemplified by for instance by the discovery of the PARP inhibitor treatment in BRCA mutated cancers, MTH1 and OGG1 inhibitors along work on replication stress in cancer. Dr Helleday has received numerous international awards and prizes such as; the Eppendorf-Nature Young European Investigator Award 2005, the European Association for Cancer Research Young Cancer Researchers Award 2007, the Swiss Bridge Award 2008, the Svedberg Award 2008, Carcinogenesis Young Investigator Award 2010 and ERC Advanced Grant Awards (2010 and 2016).
Materials Science and Engineering and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, USA
"We seek to establish a technology that yields a quantitative description of signal transduction across the plasma membrane, and apply it to study the activation of receptor tyrosine kinases (RTKs). The 58 different human RTKs regulate cell growth and differentiation. They play a critical role in human development and in adult life. RTK dysfunction leads to uncontrolled growth (as in cancer) or to impeded growth (as in dwarfism or other developmental syndromes). I will describe measurements of RTK phosphorylation efficiencies, as given by the so-called “transducer function”, which links the phosphorylation (the response) and the ligand-receptor binding events (the stimulus). The new technology can provide new insights into the mechanism underpinning differential signaling of receptor tyrosine kinases in response to different ligands, an unsolved basic biological problem with implications for therapeutics development."
Kalina Hristova received her Ph.D. degree in Mechanical Engineering and Materials Science from Duke University, USA. She is a Professor of Materials Science and Engineering at the Institute for NanoBioTechnology at Johns Hopkins University. Dr. Hristova is the recipient of the 2007 Margaret Oakley Dayhoff award from the Biophysical Society. She was elected Fellow of the American Physical Society in 2016, and Fellow of the American Institute for Medical and Biological Engineering in 2018. She was an elected 2014-2017 Biophysical Society Council member and is currently the Treasurer of the Biophysical Society. The main focus of the research in her laboratory is the physical principles that underlie membrane protein folding and signal transduction across biological membranes.
Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany
"Cells organize many of their biochemical reactions by formation and dissolution of non-membrane-bound compartments. Recent experiments show that a common mechanism for such biochemical organization is phase separation of unstructured proteins to form liquid-like compartments, which can subsequently harden to form compartments with new material properties such as gels and glasses. These compartments can be described by principles elucidated from condensed-matter physics and are therefore termed biomolecular condensates. I will discuss potential roles of phase separation in organization of cellular biochemistry and the role of aberrant phase separation in disease. I will also describe how these discoveries were facilitated by the establishment of the Max Planck Institutes for Cell Biology and Genetics and the Physics of Complex systems, in Dresden."
Prof. Dr. Anthony Hyman is Director and Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics. He was born May 27, 1962 in Haifa, Israel and is a citizen of the UK. In 1984, he received his BSc first class in Zoology from the University College in London, where he worked as research Assistant in 1981. From 1985 to 1987 he wrote his PhD on “The establishment of division axes in early C.elegans embryos” under the supervision of Dr. John White at the Laboratory of Molecular Biology, MRC in Cambridge, England. From 1988-1992 he carried out his postdoctoral research in the lab of Prof. Tim Mitchison at UCSF, investigating the mechanism of chromosome movement with in vitro approaches. In 1993, he became a Group Leader at the European Molecular Biology Laboratory in Heidelberg, before he moved to Dresden in 1999 as one of the founding directors of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), where he remains a Director and Group Leader today. He was Managing Director of the MPI-CBG from 2010-2013. Dr. Hyman has received a number of awards and honors throughout his career. As a postdoc, Dr. Hyman was a Lucille P. Markey Senior Fellow (1991-1992). He has been a member of ASCB since 1996 and EMBO since 2000. In 2002, Hyman was named honorary Professor of Molecular Cell Biology at the Technical University Dresden. He was awarded the EMBO Gold Medal in 2003, and he was elected as a Fellow of the Royal Society in 2007. In 2011, Dr. Hyman was awarded the Gottfried Wilhelm Leibniz Prize, the most important research award in Germany. Most recently, in 2017, he was honored to receive the Schleiden Medal from the German National Academy of Sciences Leopoldina. This award is given once every two years for outstanding findings in the field of cell biology. Also in 2017 the American Society for Cell Biology presented Lifetime Fellow Recognition to Prof. Dr. Hyman for distinguished contributions to the advancement of cell biology.
In 2019 Prof. Hyman was awarded the Carl-Zeiss-Lecture for outstanding achievements in Cell Biology by the German society for Cell Biology. Furthermore, in 2020 he was again honored to receive yet another award: The Wiley Foundation Prize in Biomedical Science.
The Jensen Laboratory, Division of Biology and Biological Engineering, Caltech, Pasadena, USA
"In the last ten years electron cryotomography (cryo-ET) has made it possible to visualize large macromolecular assemblies inside intact cells in a near-native, "frozen-hydrated" state in 3-D to a few nanometers resolution. Increasingly, atomic models of individual proteins and smaller complexes obtained by X-ray crystallography, NMR spectroscopy, or other methods can be fit into cryotomograms to reveal how the various pieces work together inside cells. To illustrate these points, I will present examples of current results such as our recent work on the HIV-restriction protein Trim5α and the unfolded protein response sensor IRE1α, both of which form polymers inside cells. I will also show how cryo-ET can be used to reveal the ultrastructures of bacteria, including pathogens."
Grant Jensen is a Professor of Biochemistry and Dean of the College of Physical and Mathematical Sciences at Brigham Young University (BYU) in Provo, Utah. He earned his doctorate working on electron microscopy of RNA polymerase and other protein complexes with Dr. Roger Kornberg (who later won the Nobel prize for structural studies of transcription) at Stanford University. Next Grant continued his work in protein electron microscopy as a Damon Runyon-Walter Winchell post-doctoral fellow under the supervision of Dr. Kenneth Downing at the Lawrence Berkeley National Lab. There his interests expanded to include electron tomography of whole cells. Grant began his independent career at the California Institute of Technology (Caltech) in 2002. At Caltech his research has focused on three main areas: the ultrastructure of small cells, the structural biology of HIV, and the further development of cryo-EM technology. Together with his colleagues he has now published nearly 200 papers in these areas (see http://www.jensenlab.caltech.edu/publications.html). His lab has developed a searchable tomography database and populated it with ~50 thousand cryotomograms of over 100 different viral and microbial samples (https://etdb.caltech.edu/). Among his most prominent discoveries has been the structure and function of the bacterial type VI secretion system, a "poison-tipped spring-loaded molecular dagger," and the architecture of the type IV pilus responsible for cell motility. All this work is now summarized in an electronic textbook, the Atlas of Bacterial and Archaeal Cell Structure (https://www.cellstructureatlas.org/). Meanwhile Grant’s teaching has centered on biophysical methods, including the creation of the popular online course Getting started in Cryo-EM (http://cryo-em-course.caltech.edu/). In 2020 Grant moved to BYU to become Dean of their College of Physical and Mathematical Sciences.
Max-Planck-Institute for Biology of Ageing, Cologne, Germany
"Mitochondria are central metabolic hubs whose structure and function dynamically adapt to changing metabolic demands and environmental challenges. Metabolic reprogramming of mitochondria occurs during development, cell differentiation, in ageing and disease and is coupled to changes in mitochondrial mass and shape. Similarly, stress conditions and altered metabolic cues induce mitochondrial adaptations, altering proteostasis and lipid homeostasis of mitochondria. The group aims at a mechanistic understanding of mitochondrial plasticity at the cellular and organismal level and examines how disturbances in the dynamic behavior of mitochondria affect ageing and age-associated diseases, such as neurodegeneration, cardiomyopathies and cancer.
Proteases residing in mitochondria are emerging as central regulators of mitochondrial plasticity. The i-AAA protease YME1L regulates mitochondrial biogenesis, morphology and metabolism. In response to hypoxia or nutrient starvation, inhibition of mTORC1 induces a phospholipid signaling cascade triggering YME1L activation and proteolytic rewiring of mitochondria. YME1L-mediated proteolysis repurposes mitochondria from supporting oxidative phosphorylation and ATP synthesis to promoting anaplerotic reactions that ensure the synthesis of nucleotides. While YME1L activation promotes growth of pancreatic ductal adenocarcinoma cells, tissue-specific loss of YME1L causes mitochondrial fragmentation and is associated with heart failure and neurodegeneration in mice. Nucleotide deficiencies upon loss of YME1L trigger the release of mitochondrial DNA to the cytosol, where it elicits an innate immune response along the cGAS-STING-TBK1 pathway. Our results thus identify inflammatory responses induced by the release of mitochondrial DNA as a metabolic response to nucleotide deficiency and highlight the regulatory role of a mitochondrial protease at the interface of mitochondrial metabolism, morphology and inflammation."
Thomas Langer earned his PhD from the Ludwig Maximilian University Munich for work on chaperone-mediated protein folding. After working at the Memorial Sloan Kettering Cancer Center in New York, he established an independent junior group focusing on mechanisms of mitochondrial quality control. In 2001, he was appointed as professor at the Institute for Genetics of the University of Cologne and since 2018 he is director at the Max Planck Institute for the Biology of Ageing in Cologne. The group studies mitochondrial plasticity at the cellular and organismal level and examines how mitochondrial deficiencies affect ageing and age-associated diseases, such as neurodegeneration, cardiomyopathies and cancer.
Molecular Biology and Genetics Unit, Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India
"Autophagy is an evolutionary conserved, catabolic process wherein unwanted and excess cellular contents are degraded inside vacuole or lysosomes. This is brought about by capturing the cargo in double membranous vesicles called autophagosomes, which then fuse with lysosomes and deliver the contents for degradation. The rate at which cargo capture, delivery to lysosomes, and degradation take place is called “autophagy flux.” Autophagy has several implications in health and disease, and therefore, modulation of autophagy flux is very important. In my lab, we employ chemical biology and genetics approaches to understand the mechanism of different stages of autophagy flux. I will highlight the identification of two protein complexes- septin and exocyst through an unbiased genetic screen. While septins migrate from bud-neck to PAS and form novel ring-like structures around autophagosomes, the exocyst subunit form an autophagy-specific sub-complex. Both these complexes were found to regulate Atg9 trafficking and were involved in autophagosome biogenesis during autophagy prevalent conditions. Further, I will also discuss about our recent findings where we identified two compounds by unbiased chemical screening: an inhibitor that inhibits loading of Syntaxin17 on autophagosomes and the other compound that acts as xenophagy inducer restricting replication of Salmonella in TFEB dependent but mTOR independent manner."
Ravi Manjithaya received his PhD degree studying Post-transcriptional Gene Regulation from Indian Institute of Science (Advisor: Prof. Rajan Dighe). He did his postdoctoral training in the autophagy related pathways at the University of California, San Diego (Mentor: Prof. Suresh Subramani) before joining JNCASR in 2011. He was a Wellcome Trust-DBT Intermediate fellow (2011-2016). He lab is interested in understanding the mechanisms that govern autophagy and related pathways in health and disease. He was a Wellcome Trust-DBT Intermediate fellow (2011-2016). He has received the CDRI Award 2020 for Excellence in Drug Research in Life Sciences category and S Ramachandran-National Bioscience Award for Career Development by the Department of Biotechnology, Government of India.
Max-Planck-Institute for Developmental Biology, Tübingen, Germany
"Colour patterns are prominent features of most animals; they are highly variable and evolve rapidly leading to large diversities between species even within a single genus. As targets for natural as well as sexual selection, they are of high evolutionary significance. The zebrafish (Danio rerio) displays a conspicuous pattern of alternating blue and golden stripes on the body and on the anal- and tailfins. Pigment cells in zebrafish – melanophores, iridophores and xanthophores – originate from neural crest-derived stem cells associated with the dorsal root ganglia of the peripheral nervous system. Clonal analysis indicates that these progenitors remain multipotent and plastic beyond embryogenesis well into metamorphosis, when the adult colour pattern develops. The proliferation of pigment cells is regulated by competitive interactions among cells of the same type. An even spacing involves collective migration and contact inhibition of locomotion of the three cell types distributed in superimposed monolayers in the skin. This mode of colouring the skin is probably common to fish, whereas different patterns emerge by species specific cell interactions among the different pigment cell types. These interactions are mediated by channels involved in direct cell contact between the pigment cells, as well as cues provided by the tissue environment.
The colour patterns in closely related Danio species are amazingly different; their variation offers a great opportunity to investigate the genetic and developmental basis of colour pattern evolution in vertebrates. Exciting technical developments of the recent years, especially the novel possibilities of genome editing with the CRISPR/Cas9 system, allow to easily expand from model organisms into other species and directly test the function of genes by targeted knock outs and allele replacements. Thus, models and hypotheses about pigment pattern formation derived from zebrafish can now be tested in other Danio species. These studies will lay the foundation to understand not only the genetic basis of colour pattern variation between Danio species, but also the evolution of colour patterns in other vertebrates."
From 1985 until 2014 Christiane Nüsslein-Volhard was a director at the Max Planck Institute of Developmental Biology at Tübingen.
For the discovery of genes that control development in animals and humans, and the demonstration of morphogen gradients in the fly embryo she received a number of awards and honours, among others in 1995 the Nobel Prize for Medicine or Physiology together with Eric Wieschaus and Edward Lewis.
To support women with children in science she founded the Christiane-Nüsslein-Volhard-Stiftung in 2004.
Presently she is leading an emeritus research group at the Max Planck Institute of Developmental Biology at Tübingen, focusing on the formation of the colour patterns of fishes.
Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria
"Molecular machines like the ribosome are produced in large quantities during oogenesis and, similar to mRNAs, stockpiled in the quiescent egg to be readily available during embryogenesis. While the overall number of ribosomes per embryo remains constant throughout early embryogenesis, translational activity increases, suggesting that translation is repressed in the mature egg. How translation is regulated during the egg-to-embryo transition has so far been mostly investigated with an mRNA- and translation factor-centric view. However, how ribosomes are stored for extended amounts of time in the mature egg, and whether the ribosome itself contributes to the change in translational activity during embryogenesis, is currently unknown.
We discovered a new mechanism of translational regulation at the ribosome itself during the egg-to-embryo transition. Using polysome gradient, mass-spectrometric, and CryoEM analyses of ribosomes isolated from zebrafish eggs and early embryos, we find that ribosomes change from a ‘dormant’ to a translationally active state during the first hours of embryogenesis. This awakening of the ribosomes is characterized by the dissociation of a core set of four conserved factors, which are stably bound to the dormant ribosomes in the egg. These four factors block important interaction sites, such as the polypeptide exit channel, the mRNA entry channel and the peptidyl transferase center. Strikingly, some of these factors had never been associated with ribosome binding and/or translational regulation. Functional analyses of zebrafish knockout mutants and in vitro translation assays reveal a key role of these factors in increasing ribosome stability in the egg and inhibiting translation. Analysis of ribosomes from Xenopus eggs and embryos identified the same set of factors bound to the egg ribosomes, suggesting that this previously unrecognized dormant state of the egg ribosome might be universally conserved in vertebrates."
Andrea Pauli studied biochemistry in Regensburg, Germany, and obtained her Masters in Molecular and Cellular Biology from Heidelberg University, Germany. In 2004, she started her PhD at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria, co-supervised by Kim Nasmyth and Barry Dickson to investigate non-mitotic functions of cohesin using Drosophila as a model organism. In 2006, she moved with Kim Nasmyth to Oxford University, UK, where she became an avid rower and obtained her PhD in 2009, providing the first direct evidence that cohesin has essential functions in post-mitotic cells.
As a postdoc in Alex Schier’s lab at Harvard University, USA, Dr. Pauli made two key findings that have shaped her research since: first, translation is widespread outside of protein-coding regions in vertebrates; and second, some of the newly discovered translated regions encode functionally important short proteins, one of which is Toddler, an essential signal for mesodermal cell migration during gastrulation. In 2015, Dr. Pauli established her own lab at the IMP in Vienna, Austria, with a current focus on (1) the mechanism of vertebrate fertilization and (2) translational regulation during the egg-to-embryo transition. The long-term vision of the Pauli lab is to unravel new concepts and molecular mechanisms governing this fascinating developmental transition that marks the beginning of life.
Dr. Pauli’s work has been funded by EMBO, HFSP, the NIH grant to independence (K99), the FWF START Prize, a Whitman Center Fellowship from the Marine Biological Labs and the EMBO Young Investigator Program (EMBO YIP).
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
"During lineage commitment, cells sustain cascades of gene activation and repression to generate specific cell types that execute specialized functions. To investigate the variability of the 3D conformation of the genome in different cell types and their relation with cell-type specific patterns of gene expression, we applied Genome Architecture Mapping is specific brain cell types from the adult murine brain, without disturbing their native tissue environment: dopaminergic neurons (DNs) from the midbrain, pyramidal glutamatergic neurons (PGNs) from the hippocampus, and oligodendrocyte lineage cells (OLGs) from the cortex. We discover extensive reorganization of genome topology, which the reorganization of topological domains, chromatin compartments and specific long-range contacts. We also discover events of extensive chromatin decondensation, or ‘domain melting’, at long neuronal genes when they are highly transcribed, many of them associated with neurodevelopmental disorders or neurodegeneration. Our work shows that the 3D organization of the genome is highly specific of cell type and strongly related with gene expression programs."
Ana Pombo investigates mechanisms that regulate 3D genome folding and gene expression during mammalian development and in disease. After her doctorate work at the University of Oxford (UK), Ana was a recipient of a Royal Society Dorothy Hodgkin Fellowship. She started her independent group in 2000, at the MRC London Institute for Medical Sciences, Imperial College London, before moving to the max delbrück Center for Molecular Medicine in Berlin, in Germany. Ana received the Robert Feulgen Prize in 2007, and was elected EMBO member in 2018.
Department of Neurobiology, Wise Faculty of Life Sciences & Sagol School of Neuroscience, Tel Aviv Univeristy, Tel Aviv, Israel
"In C. elegans nematodes, small RNAs enable transmission of epigenetic responses across multiple generations, independently of changes to the DNA sequence. Different environmental challenges, including exposure to viruses and bacteria, starvation, and heat stress generate heritable small RNA responses, that in certain cases could be adaptive. Recently we have shown that neuronal activity can also produce small RNA-mediate heritable responses. The precise duration of small RNA-mediated transgenerational responses is governed by a number of feedback interactions, that together establish a “timer” mechanism, and segregation of the epigenetic response between the descendant obeys a few simple inheritance rules.
One of the biggest mysteries in the field is whether heritable small RNA responses can impact the process of evolution. In this talk I will present new results that address this question. By studying nematodes that choose whether to self-reproduce or outcross, we show that inherited small RNAs affect sexual attraction and mating for multiple generations and thus indirectly control genetic variation. We found that manipulating endogenous small RNA levels in hermaphrodites induces premature secretion of a male-attracting pheromone, increases the prevalence of males, and ultimately elevates the rate of successful mating. Further, stress leads to enhanced sexual attraction which transmits transgenerationally for three generations. Simulations and multigenerational competition experiments demonstrate that the rise in mating, driven by heritable small RNAs that promote sexual attraction, can increase alleles frequencies in the population. This non-DNA based inheritance process could be a mechanism for elevating the rate of outcrossing in challenging environments, when increasing genetic variation is advantageous."
Oded Rechavi is a Full Professor in the Life Sciences Faculty at Tel Aviv University. His mission is “to challenge fundamental long-held scientific dogmas”. Using C. elegans nematodes he provided direct evidence that an acquired trait can be inherited, worked to elucidate the mechanism and rules of small RNA-mediated transgenerational inheritance, discovered that the nematodes’ brains can control the behavior of their progeny, and identified a simple neuronal circuit-level mechanism that explains economic irrationality. Aside from his work on nematodes, Oded utilized genome sequencing of ancient DNA to “piece together” fragments of the Dead Sea Scrolls and demonstrated that Toxoplasma parasites can be genetically engineered to deliver drugs to the nervous system. He is an ERC Fellow, and was awarded many prestigious prizes, including the Polymath prize (Schmidt Futures), the Kadar award, the Blavatnik award, the Krill Wolf award, the Alon, and F.I.R.S.T (Bikura) Prizes, and the Gross Lipper Fellowship. Prof. Rechavi was selected as one of the “10 Most Creative People in Israel Under 40”, and one of the “40 Most Promising People in Israel Under 40”.
Department of Plant Pathologt and the Genome Center, UC Davis, Davis, USA
"Professor Pamela Ronald is recognized for her discovery of rice genes controlling resistance to infection and tolerance to submergence. Submergence tolerant, climate-resilient rice varieties are widely grown by millions of subsistence farmers in India and Bangladesh. Ronald also contributed to the development of a CRISPR-Cas9-based targeted gene insertion method to deliver gene cassettes into genomic safe harbors in rice. Using this method, the Ronald lab obtained rice plants with high carotenoid content in the seeds. These studies offer promising strategies for genetic improvement of rice and other crops."
Pamela Ronald completed her Ph.D. at UC Berkeley (1990), earned a B.S. from the Reed College (1982), an M.S. from Stanford University and an M.S. from the University of Uppsala, Sweden. Prof Ronald uses genetic techniques to understand the plant response to infection and tolerance to environmental stress. With her collaborators, she received the 2008 USDA National Research Initiative Discovery Award and the 2012 Tech Award for the innovative use of technology to benefit humanity. In 2015 Scientific American named her one of the 100 most influential people in biotechnology. Ronald’s book, Tomorrow’s Table: Organic farming, Genetics and the Future of Food was selected as one of a 25 most influential books with the power to inspire college readers to change the world. Her 2015 TED talk has been viewed by more than 1.9 million people and translated into 26 languages. In 2019, she received the American Society of Plant Biologists Leadership Award, an honorary doctorate from the Swedish Agricultural University and was elected to the National Academy of Sciences. In 2020 she was named a World Agricultural Prize Laureate by the Global Confederation of Higher Education Associations for Agricultural and Life Sciences.
The Eugene Bell Center, Marine Biological Laboratory, The University of Chicago, Woods Hole, USA
"Genetic information is stored in DNA and realized in proteins after passing through RNA. Its transient residence in RNA provides a prime opportunity for modification. Changes in DNA are permanent and perilous; those in RNA go away, making them safer. There are a variety of systems for altering RNA in cells. Alternative splicing, of course, is a well-studied example. My lab focuses on RNA editing through adenosine deamination, a system for introducing point mutations within RNA. All multicellular metazoans use this system, but cephalopods take it to a new level, particularly in their nervous system. I will discuss how cephalopods use RNA editing, the messages that are targeted, where it is taking place within neurons, and how it can respond to environmental cues."
Joshua Rosenthal is a Senior Scientist at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts. He received his Ph.D. in Biology from Stanford University and completed his postdoctoral training in biophysics and physiology at UCLA. Before coming to the Marine Biological Laboratory, he rose from Assistant to Full Professor at the University of Puerto Rico’s Medical Sciences Campus. Dr. Rosenthal’s research focuses on the process of RNA editing from a variety of angles. His group has shown that mRNA recoding is unusually active in cephalopods. They are interested in what it’s being used for and how the underlying machinery for RNA editing differs in this taxon. Other projects aim to use RNA editing as a vehicle for therapeutics. Finally, Rosenthal also leads an initiative at the MBL to create genetically tractable marine model organisms.
Neurology, F. M. Kirby Neurobiology Center, Boston Children's Institute, Boston, USA
Neurobiology, Harvard Medical School, Cambridge, USA
"The kinetochore has been studied intensively for its role in cell division where it forms the load-bearing junction between microtubules and centromeres. It is essential for accomplishing the proper segregation of chromosomes to daughter cells and is also the nexus for regulating chromosome mechanics. In a forward genetic screen for mutations of synapse formation at the Drosophila neuromuscular junction, we identified mutations in the kinetochore component mis12 as responsible for the failure to form proper synaptic boutons and neurite branching on targets. Subsequent genetics determined that most of the core components of the kinetochore, including the microtubule-binding subunit Ndc80 gave similar phenotypes. In cultured mammalian neurons, knockdown or mutation of kinetochore components alters the formation of dendritic spines and axonal growth cones. The kinetochore is present in axons, dendrites, growth cones, and synapses and regulates the dynamics of microtubule + end growth. Neuronal microtubules are typically stable; the kinetochore now emerges as a regulator of microtubule dynamics in post-mitotic neurons that can govern the number and properties of synaptic contacts."
Thomas L. Schwarz is Assistant Director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, Professor of Neurology at Harvard Medical School, and is appointed as an Excellence Chair at the University of Bremen. He holds an A.B and Ph.D from Harvard University and was previously on the faculty at Stanford Medical School. Since his postdoctoral work at UCSF on the cloning of the Shaker K+ channel, his lab has combined genetics and cell biology to study neurons. His laboratory has used mutations that alter the formation and function of synapses, including mutations of synaptic vesicle and cell surface proteins and components of endocytic pathways. They discovered that α2δ proteins are required for proper synaptic bouton formation independent of their Ca channel function and recently demonstrated that proteins of the kinetochore complex are repurposed in post-mitotic neurons to influence synapse formation. Another major focus of the laboratory is the axonal transport of mitochondria; they described the motor/adaptor complex that governs that transport, investigated pathways that regulate mitochondrial motility, and examined the significance of defects in mitochondrial transport for neurodegenerative diseases.
Ruđer Bošković Institute, Zagreb, Croatia
"At the onset of division the cell forms a spindle, a micro-machine made of microtubules, which divide the chromosomes by pulling on kinetochores, protein complexes on the chromosome. The central question in the field is how accurate chromosome segregation results from the interactions between kinetochores, microtubules and the associated proteins. We have shown that a bundle of antiparallel microtubules, termed “bridging fiber”, connects sister kinetochore fibers in human spindles. Bridging microtubules are linked together by the protein regulator of cytokinesis 1 (PRC1). To explore the role of bridging fibers in chromosome movements, we developed an optogenetic approach to remove PRC1 from the spindle to the plasma membrane in a fast and reversible manner. These experiments showed that bridging fibers promote chromosome alignment at the metaphase plate by forces that depend on the microtubule overlap within the bridging fiber. By combining a theoretical model with superresolution imaging of the bridging fibers, we discovered that they are twisted in the shape of a left-handed helix, making the spindle a chiral object. This finding suggests that torques exist in the spindle in addition to linear (pushing and pulling) forces. During anaphase, bridging microtubules promote chromosome segregation by sliding apart, which is driven by the motor activity of kinesin-4 and kinesin-5. Understanding the role of bridging microtubules in force generation and chromosome movements not only sheds light on the mechanobiology of a well-functioning spindle, but will also help to understand the origins of errors in chromosome segregation."
Iva Tolić is a Professor of Biology and Senior Research Group Leader with tenure at the Ruđer Bošković Institute in Zagreb, Croatia. She graduated in molecular biology from the University of Zagreb. Her PhD work on cell mechanics was done with Prof. Ning Wang at Harvard. Afterwards, she did a postdoc in cell biophysics with Prof. Kirstine Berg-Sørensen at the Niels Bohr Institute in Copenhagen, Denmark, and later with Prof. Francesco Pavone at LENS - European Laboratory for Non-Linear Spectroscopy, in Florence, Italy. From 2004 until 2014 she worked as a Research Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany. In 2015, she returned to her hometown Zagreb. Her research areas are biophysics of the spindle in mitosis and meiosis, microtubules and motor proteins.
Iva is a recipient of the prestigious grants funded by the European Research Council (ERC), Consolidator and Synergy. She has been elected to EMBO membership. In 2014, she was chosen by the journal Cell as one of 40 scientists from around the world and working in diverse biological fields, "40 under 40". She received numerous awards such as the Ignaz Lieben Award of the Austrian Academy of Sciences, European Biophysical Societies Association (EBSA) Young Investigators' Medal and Prize, European Life Science Award in the category Investigator of the Year, Croatian Women of Influence Award, and National Science Award of the Republic of Croatia.
Hutment Laboratory, Tata Institute of Fundamental Research, Mumbai, India
Vidita received her undergraduate training in Life Science and Biochemistry at St. Xavier’s College in Mumbai. She obtained her doctoral degree in Neuroscience at Yale University, and after postdoctoral fellowships at the Karolinska Institute and Oxford University she returned to a faculty position at the Tata Institute of Fundamental Research in 2000. She has been a Senior Overseas Wellcome Trust Fellow and is a fellow of the Indian National Science Academy. She received the National Bioscientist Award in 2012 and the Shanti Swarup Bhatnagar Award in Medical Sciences in 2015. Her research group is interested in understanding the neurocircuitry of emotion, its modulation by life experience and the alterations in emotional neurocircuitry that underlie complex psychiatric disorders like depression.
Harvard Department of Stem Cell and Regenerative Biology, Harvard Medical School, Cambridge, USA
"Human limitations in natural regeneration can dramatically affect a patient's life, such as after limb loss. Axolotl salamander limbs that are anatomically similar to human limbs, but they can perfectly regenerate throughout life. Understanding how this happens may provide important clues necessary for future therapeutic approaches. While most research has focused on the site of injury, we have discovered that cells throughout the axolotl's body activate and proliferate following amputation. This process of systemic activation is akin to what other researchers have discovered to happen in mice following a local injury. However, mice do not go on to regenerate entire limbs. We will present data demonstrating that some of the molecular mechanisms that enables systemic response is mice and shared with axolotls. Elucidating how the systemic response occurs
in axolotl will be key to understanding how cells are initially systemically activated, while only those at the site of injury are converted to blastema cells, those cells that are the building blocks for the new limb. Our unpublished work shows that innervation at distantly-responding sites is critical for the systemic injury response in axolotls. This work has led us to consider molecular factors derived from nerves as stimulants for activation pathways in tissue-specific progenitor cells residing throughout the body. A nerve conduit for the response contrasts with the circulation conduit implicated in mouse, raising questions about how information is transmitted throughout the body in super-regenerators versus animals with more limited natural regenerative abilities. We hope this work will lead to both molecular insights as well as theoretical insights about the differences between species when considering regeneration and, ultimately, how human regeneration might be augmented."
Jessica holds a BA in Philosophy and a BS in Biological Sciences from the University of Missouri. She earned her PhD at MIT, where she studied neuronal architecture in Paul Garrity's lab. As a postdoc in Cliff Tabin's lab at Harvard Medical School, Jessica focused on developing tools to more thoroughly investigate axolotl limb regeneration, and she established a breeding colony of axolotls. These animals were the seeds of the Whited Lab's first home in Brigham and Women's Hospital. Now at Harvard University, Jessica is an Assistant Professor, a Principal Faculty member of the Harvard Stem Cell Institute, an Associate Member of the Broad Institute, a Smith Family Foundation fellow, a March of Dimes Basil O'Connor Scholar, an NIH New Innovator Awardee, and the recipient of the Presidential Early Career Award for Scientists and Engineers (PECASE). Her lab is mainly focused on understanding how injury responses are translated into tissue regeneration through formation of a blastema structure. A native of Michigan, Jessica's interest in biology started with butterflies and time in the woods. Outside of lab, Jessica's usually hanging out with her twin 11-year-old boys.