International Invited Speakers
Liran Carmel did a PhD in applied mathematics at the Weizmann Institute of Science, Israel. Since 2008, he is at the Hebrew University of Jerusalem, where he is now a professor of computational biology. Liran has won many awards, including the Michael Milken prize, the Farkash award and the Eshkol fellowship.
Liran is studying a host of topics in molecular evolution, RNA biology and genetics and is particularly interested in human evolution and in understanding what makes us human. In recent years, Liran has been studying ancient DNA of anatomically modern humans, archaic humans (Neanderthals and Denisovans), mammoth and more. He developed a technique to reconstruct DNA methylation maps along ancient genomes, thus allowing the discovery of evolutionary changes in gene regulation. He showed that such regulatory changes underlie many of the human-specific traits, such as the unique architecture of our voice box. He also used these regulatory changes to suggest the first anatomical reconstruction of the little-known Denisovan, as well as to probe into the environments in which these ancient individuals lived.
Many nuclear DNA-binding proteins also bind RNA, often inexplicably. For example, the histone methyltransferase Polycomb Repressive Complex 2 (PRC2) binds nuclear RNAs with high affinity and limited specificity, but it has been highly controversial whether these interactions are functionally important. We have used CRISPR-Cas9 genome editing, live cell single molecule imaging, and genome-wide and transcriptome-wide experiments to reveal the importance and the mechanism by which RNA binding regulates PRC2 recruitment to target genes.
The universality of eukaryotic chromosome linearity suggests some evolutionary advantage, despite the clear challenges imposed by linear chromosome ends, whose vulnerability to degradation and end-joining pathways drives genome instability. We have uncovered key principles underlying the ability of telomeres to protect chromosomes from these threats, and identified unforeseen additional telomeric roles, including the control of meiotic nuclear envelope breakdown and centromere assembly. These discoveries provide novel rationales for the evolutionary persistence of chromosome linearity. Furthermore, we find instances in which telomeres and other genomic regions can function interchangeably, an initially counter-intuitive finding with implications for genome plasticity and evolution.
Dr. Christina Curtis is faculty at Stanford University School of Medicine, where she leads the Cancer Computational and Systems Biology Group and is Co-director of the Molecular Tumor Board. Dr. Curtis’ research leverages genome-scale data, computational modeling and iterative experimentation to delineate mechanisms of tumor progression and to develop predictive and prognostic biomarkers. Her research has led to new paradigms in understanding how human tumors evolve and has redefined the molecular taxonomy of breast cancer. Dr. Curtis is a National Academy of Sciences Kavli Frontier of Science Fellow and recipient of the 2018 NIH Director’s Pioneer Award.
Our group investigates chromosome organization and dynamics. We focus on meiosis, the specialized cell division process that gives rise to reproductive cells such as sperm, eggs, pollen, and spores. Meiotic errors underlie many human birth defects such as Down Syndrome, and also contribute to human infertility, especially in older women. Successful meiosis requires a unique series of chromosome interactions: each chromosome must pair with its homologous partner, and these paired chromosomes then exchange genetic information through homologous recombination. Crossover recombination gives rise to genetic diversity, and also creates physical links between chromosomes that enable them to segregate away from each other. We investigate these mechanisms using the nematode Caenorhabditis elegans as our primary model organism. This experimental system has enormous experimental advantages, including rapid and powerful genetics, robust genome editing, outstanding cytology, and the opportunity to directly observe meiosis through in vivo imaging.
Dr. Durocher’s research interests lie in understanding how cells maintain genome integrity, with an emphasis on the detection, signaling and repair of DNA lesions such as DNA double-strand breaks. Dr. Durocher’s work has recently expanded to include large-scale mapping of the genetic networks surrounding the response to DNA damage, in an effort to uncover new genes and process that influence genomic integrity, and to identify new therapeutic targets in oncology.
For the past 25 years, Anne Ferguson-Smith’s team has studied epigenetic inheritance and its role in mammalian development with a focus on genomic imprinting and the epigenetic control of genome function. This work has also contributed more generally to understanding pathways controlling developmental and physiological processes including neurogenesis and metabolism, and to a greater understanding of mechanisms regulating both dynamic and heritable epigenetic states. Most recently her team has identified a repertoire of mammalian epialleles associated with repetitive elements which exhibit inter-individual epigenetic variation. The function, properties and inheritance of these epialleles is currently being investigated.
Anne is the Arthur Balfour Professor of Genetics and Head of the Department of Genetics at the University of Cambridge. She was elected to EMBO in 2006, to the Academy of Medical Sciences in 2012 and as a Fellow of the Royal Society in 2017.
The Gilad Lab is focused on moving beyond simple explorations of gene expression levels, to studies of variation in regulatory mechanisms, response phenotypes, and ultimately – complex traits (including disease). Our lab uses multiple complementary approaches to characterize variation in genetic and epigenetic regulatory mechanisms within and between species. By integrating gene expression data from multiple tissues and cell types with epigenetic profiles, chromatin states, post-transcriptional modifications, and other molecular data, we can generate specific hypotheses about regulatory mechanisms and learn about their relative importance for different molecular and phenotypic outcomes.
Research in our laboratory is focused on the epigenetic control of higher-order chromatin assembly. The dynamic regulation of higher-order chromosome structure governs diverse cellular processes ranging from stable inheritance of gene expression patterns to other aspects of global chromosome structure essential for preserving genomic integrity.
Eva Hoffmann is professor in genomics and reproductive health at the Medical School, University of Copenhagen, Denmark. Her lab investigates genome diversification processes in the human germline using single-cell and low-input genomics, in particular meiotic recombination and chromosome segregation and their impact on genome stability and pregnancy loss. She serves on the executive board of ReproUnion (www.reprounion.eu) and is funded by the ERC and Novo Nordisk Foundation.
Our studies are focused on understanding inheritance, chromatin structure, gene expression, and the organization of chromosomes in the nucleus. Most of our studies have focused on the fruit fly Drosophila melanogaster as a model for chromosome function in metazoans, which allows us to address mechanisms in animals by synergistically combining molecular, genetic, cell biological and biochemical approaches. Additionally, we have examined the relevance of our findings to human chromosomes, and have demonstrated surprising similarities between these evolutionarily-distant species.
Dr. Klein studies how cells make fate choices in developing and adult tissues, specializing in mapping differentiation hierarchies and their fate control. He developed droplet microfluidics for single-cell RNA-Seq (inDrop), computational methods for analyzing single-cell data sets, and methods for quantitative clonal analysis. He focuses on the early embryo, epithelial tissues and the hematopoietic system as model systems.
The aims of our research are to understand how DNA double-strand breaks (DSBs) are repaired in the context of chromatin and what dictates the repair pathway choice. DSBs are mainly repaired by either Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). When inaccurately used, these repair pathways have dramatically different consequences on the genome; for example, translocations mainly caused by Alt-NHEJ, or repeat amplifications provoked by the use of unequal HR. The choice between all the available pathways is thus a critical aspect of DSB repair. However, how this choice is executed is far from being understood. To address the molecular mechanisms at play, we developed the DIvA cell line which is a powerful experimental cell system that enables the creation of DSBs at well-known positions across the genome in various chromatin contexts and which has the advantage of detaining statistical power over a large range of DSBs.
New technologies to sequence RNA and DNA from individual cells are providing unprecedented insights into the biology of complex tissues. We use single cell genomic and transcriptomic data to reconstruct differentiation pathways, lineage hierarchies, and tissue heterogeneity in human organs and organoids, mouse brains and lungs, amphibian appendages, and any other system we find fascinating! Our primary goal is to understand the mechanisms controlling cell fate decisions during development and regeneration, with a particular interest in illuminating uniquely human biology.
Our main research interests are in sex chromosome evolution, sex-biased processes, population genetics, and comparative genomics. Whereas the non-sex chromosomes (autosomes) can partner up and swap DNA over their entire lengths, the sex chromosomes, X and Y, in mammals only swap DNA on the tips. The human X and Y chromosomes evolved from a pair of homologous autosomes, but today the X has more than ten times the gene content of the Y. Which genes were lost, and how does the loss of functional genes on the Y affect the evolution of the human X? Are genes with some functions or expression patterns more likely to be retained on the Y? We study these processes and their consequences.
National Invited Speakers
To be announced