Speakers (in alphabetical order)
"Paleo-epigenetics: The use of ancient DNA methylation patterns to study human evolution"
Abstract: Changes in regulation are broadly accepted as key drivers of phenotypic divergence. However, identifying the regulatory changes that shaped human-specific traits remains poorly explored. I will show a method to reconstruct pre-mortem DNA methylation patterns in ancient genomes, and how it can be used to identify key anatomical differences between human groups (modern humans, Neanderthals and Denisovans). I will provide insights into the molecular mechanisms that may have shaped the modern human face and voice, and suggest that they arose after the split from Neanderthals and Denisovans. I will also show an anatomical reconstruction of the Denisovan, whose anatomy is virtually unknown. Finally, I will discuss how DNA methylation from bones can be used to infer DNA methylation in tissues that are not accessible in the fossil record like brain.
Bio: Liran Carmel received MSc in physics from the Technion – Israel Institute of Technology, and PhD in applied mathematics from the Weizmann Institute of Science, Israel. He then pursued postdoctoral studies in molecular evolution at the National Institutes of Health. Since 2008 Liran Carmel is at the Hebrew University of Jerusalem, where he is now a professor to computational biology. He is studying a host of topics in molecular evolution, and is particularly interested in human evolution, and in understanding what makes us human. Liran Carmel is among the founder of paleo-epigenetics, a technology to reconstruct epigenetic signals in ancient genomes, thus obtaining information on ancient gene regulation.
Keynote: "The Neurobiological Platform of Moral Conscience"
Abstract: Self-caring neural circuitry embodies self-preservation values, and these are values in the most elemental sense. Whence caring for others? The compelling line of evidence from neuroendocrinology suggests that in mammals and possibly birds, caring for others is an adaptation of brainstem-limbic circuitry whereby what counts as “me” extends to include offspring -- “me and mine”. Oxytocin is at the hub of the intricate network adaptations. In some species, strong caring for the well-being of others may extend also to include kin or mates or friends or even strangers, as the circle widens. Two additional interdependent evolutionary changes are crucial for mammalian sociality/morality: (1) modifications to the reptilian pain system that, when elaborated, yield the capacity to evaluate and predict what others will feel, know, and do, and (2) learning, strongly involving the reward system, linked to social pain and social pleasure that regulates the acquisition of the clan’s social practices and the emergence of a conscience tuned to these practices. Social problem-solving, including policy-making, is probably an instance of problem-solving more generally, and draws upon the capacity, prodigious in humans, to envision consequences of a planned action. In humans, it also draws upon the capacity for improving upon current practices and technologies. Unlike other mammals, humans have developed highly complex language, and highly complex cultures. This means that our sociality, and consequently ours systems of ethical values, have become correspondingly complex.
Bio: Patricia Smith Churchland is a Professor emerita of Philosophy at the University of California, San Diego, and an adjunct Professor at the Salk Institute. Her research focuses on the interface between neuroscience and philosophy. She is author of the pioneering book, Neurophilosophy (MIT Press 1986), and co-author with T. J. Sejnowski of The Computational Brain (MIT 1992). Her current work focuses on morality and the social brain; Braintrust: What Neuroscience tells us about Morality (2011 Princeton U P). Touching a Nerve, published by Norton in 2013, portrays how to get comfortable with this fact: I am what I am because my brain is as it is. In June 2019, her latest book was released – Conscience: The Origins of Moral Intuition. She has been president of the American Philosophical Association and the Society for Philosophy and Psychology, and won a MacArthur Prize in 1991, the Rossi Prize for neuroscience in 2008, and the Prose Prize for science for the book, Braintrust. She was chair of the Philosophy Department at the University of California San Diego from 2000-2007.
"How Nature and Nurture Conspire to Control Brain Development and Function"
Abstract: Dr. Greenberg’s research seeks to understand how neuronal activity controls gene transcription to affect critical steps in synapse and neural circuit development. In addition to providing insight into the process of brain development and evolution, this research has contributed to the understanding of neurological and psychiatric diseases in which these processes have gone awry.
Bio: Michael E. Greenberg is the Chair of the Department of Neurobiology and Nathan Marsh Pusey Professor at Harvard Medical School. He received his Ph.D. from the Rockefeller University in 1982 and carried out his postdoctoral research at New York University Medical Center. After joining the faculty at Harvard Medical School in 1986, Dr. Greenberg served first as the founding Director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and since 2008 as Chair of the Department of Neurobiology at Harvard Medical School.
"Neandertal introgression sheds light on brain evolution"
Abstract: The skulls of humans living today are characterized by a combination of features that distinguish us from our fossil relatives and ancestors: a small and gracile face, and globular braincase. Brain tissues do not fossilize, but as the brain expands during early development it leaves in an imprint in the bony braincase. Such endocranial imprints of fossil hominins make it possible to trace evolutionary changes of brain size and aspects of brain organization. Combining data from fossil skulls, brain scans of living people, and genetic data we can explore how the genotype relates to the unique brain phenotype of modern humans. To identify potential candidate genes and biological pathways that are related to endocranial globularity, we turned to our closest extinct relatives, the Neandertals. We found introgressed Neandertal alleles associated with reduced endocranial globularity affect the expression of genes linked to neurogenesis and myelination.
Bio: Philipp Gunz is a paleoanthropologist with a PhD from the University of Vienna (Austria), who works as group leader at the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany). His team’s publications explore different aspects of ontogenetic and phylogenetic shape changes — in particular the evolution and development of the brain and the imprint it leaves in the bony braincase. This research integrates recent advances in genetics, micro-CT and magnetic resonance imaging, and statistical shape analysis.
"Cortical neuron structure-function relationships across mammalian species"
Abstract: The general organization of the mammalian cortex, the engine of cognition, is highly conserved. However, single cortical neurons exhibit surprising morphological diversity across species. For example, the dendritic arbors of human pyramidal neurons are roughly 3 times the size of those in mice. In this talk, I will discuss my lab’s recent progress in evaluating how these structural differences influence the functional properties of single neurons. By comparing the biophysical properties of identified cell types in temporal cortex of multiple mammals (shrew, mouse, gerbil, rat, ferret, rabbit, marmoset, macaque, and human), we hope to gain insight into the principles that govern cortical neuron design and evolution.
Bio: Mark Harnett received his B.A. in Biology from Reed College and his Ph.D. in Neuroscience from the University of Texas at Austin. His doctoral work focused on the physiology and plasticity of midbrain dopamine neurons and their role in motivated behavior and addiction. Mark did his postdoctoral research at the Howard Hughes Medical Institute’s Janelia Research Campus with Jeff Magee, where he investigated dendritic integration in cortical and hippocampal neurons. He is now an Assistant Professor in the Department of Brain and Cognitive Sciences and an Investigator in the McGovern Institute for Brain Research at MIT. His laboratory works on how biophysical processes at the level of synapses and single neurons contribute to the neural circuit computations that guide behavior.
"Domestication as a natural experiment in brain-behavior evolution"
Abstract: Humans are characterized by an innate predisposition to acquire certain domains of learned skills, such as language and tool use. How do the underlying neural adaptations arise? Domestication offers a unique window into this question because it involves strong, sometimes intentionally-applied selection pressure on a focused set of behaviors. Furthermore, several targeted behaviors are learned and require specific experiences during developmental critical periods. This talk will present work on brain-behavior adaptations in different breeds of domestic dogs and in tame and aggressive strains of selectively-bred Siberian foxes. Links to human evolution will be discussed.
Bio: Dr. Hecht directs the Evolutionary Neuroscience Laboratory in the Department of Human Evolutionary Biology at Harvard University. Her research asks how brains change in response to selection pressure on behavior, and how brains acquire heritable adaptations for complex, learned behaviors. One line of work compares brain-behavior relationships in humans and our primate relatives. Another area of research is focused domestic dogs and selectively-bred foxes, which are other highly encephalized, social species. Techniques include structural and functional neuroimaging, behavior measurements, histology, and microscopy. Before joining the faculty at Harvard, Dr. Hecht was a Research Scientist in the Center for Behavioral Neuroscience at Georgia State University, and an Affiliated Scientist at the Yerkes National Primate Research Center at Emory University. Dr. Hecht received her B.S. in Cognitive Science from the University of California San Diego in 2006, and her Ph.D. in Neuroscience from Emory University in 2013.
"Cell type diversity in human cerebral cortex"
Abstract: Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. To classify cell types in human brain we used single-nucleus RNA-sequencing and performed a comprehensive study of multiple regions of cerebral cortex, including primary sensorimotor areas and several association areas. Comparisons of human cortical cell types to those found using similar mouse cortex single-cell RNA-sequencing datasets revealed a general conservation of the cortical cellular architecture between species punctuated by species-specific alterations in gene expression and cellular proportions.
Bio: Rebecca Hodge is a Senior Scientist in the Human Cell Types program at the Allen Institute. She joined the Allen Institute as a Scientist II in March of 2014. Prior to joining the Institute, she conducted research in the laboratory of Dr. Robert Hevner at the University of Washington and the Center for Integrative Brain Research at Seattle Children’s Research Institute. There, she studied the actions of transcription factors during the process of neurogenesis (the generation of neurons) in both the developing and adult brain. She completed herundergraduate training at Simon Fraser University in Burnaby, British Columbia where she received a Bachelor’s degree (B.Sc.) in animal physiology. Her graduate training was completed in the Department of Pathology and Laboratory Medicine at the University of British Columbia (UBC) in Vancouver, BC. Her Ph.D. work at UBC focused on the role of growth factors in regulating neural stem cell development and the generation of neurons during early development of the mammalian cerebral cortex.
Keynote: "An Adversarial Collaboration to Explore Human Consciousness"
Abstract: Humans not only act in the world but experience it, such as the delectable taste of Nutella, the sharp sting of an infected tooth, or pure experience during meditation practice or under entheogenic drugs. I will discuss progress achieved over the past decades in locating the footprints of such conscious experiences - the minimum neural mechanisms sufficient for any one specific conscious percept and will describe an adversarial and open science collaboration between the two dominant scientific schools of thought concerning human consciousness, Integrated Information Theory and Global Neuronal Workspace Theory, that make distinct predictions concerning the location and timing of the NCC in the human brain.
Bio: Christof Koch is the Chief Scientist and President of the Allen Institute for Brain Science. Christof received his baccalaureate from the Lycée Descartes in Rabat, Morocco, his B.S. and M.S. in physics from the University of Tübingen in Germany and his Ph.D. from the Max-Planck Institute for biological Cybernetics in 1982. Subsequently, he spent four years as a postdoctoral fellow in the Artificial Intelligence Laboratory and the Brain and Cognitive Sciences Department at the Massachusetts Institute of Technology. From 1987 until 2013, Koch was a professor at the California Institute of Technology (Caltech) in Pasadena, from his initial appointment as Assistant Professor, Division of Biology and Division of Engineering and Applied Sciences in 1986, to his final position as Lois and Victor Troendle Professor of Cognitive & Behavioral Biology. See here for Christof's academic pedigree and his students. Christof joined the Allen Institute for Brain Science as Chief Scientific Officer in 2011 and became President in 2015.
"Innovations in primate neuronal repertoires"
Abstract: What are the genetic, molecular and cellular bases of the (re)organization of primate brains throughout development and evolution? I will describe our efforts to compare cellular composition and gene utilization across the brains of adult mice, marmosets, macaques, and humans. Using single-cell RNA sequencing, we profiled hundreds of thousands of brain cells or nuclei and used recently developed computational methods to align datasets across species. We found evidence of four ways evolution alters the composition of a brain structure: changing proportions of conserved cell types, changing the molecular composition of conserved cell types, reallocating cell types across structures, or generating novel types. Taken together, these results reveal new insights into how relatively closely related brains diversify their cellular and molecular repertoire.
Bio: Fenna Krienen received her B.A. from UC Berkeley and completed her doctoral studies at Harvard University in Dr. Randy Buckner's lab, where she used non-invasive neuroimaging to infer principles of cortico-cortical and cortico-cerebellar network architecture in the human brain. She was a fellow at The George Washington’s Center for Advanced Study of Human Paleobiology (2014-2015) before joining Steve McCarroll’s lab as a postdoctoral fellow in Genetics at Harvard Medical School and the Broad Institute in 2015. She uses single-cell genomics technologies to explore the cellular and molecular composition of primate and rodent brains and develop a comparative framework for understanding human brain evolution.
"Establishing Great Ape Organoid Models to Study Genomic Events Contributing to Human Brain Evolution"
Abstract: Primate brains vary dramatically in size and organization, but the genetic and developmental basis for these differences has been difficult to study due to lack of experimental models. Pluripotent stem cells and brain organoids provide a potential opportunity for comparative and functional studies of evolutionary differences, particularly during the early stages of neurogenesis. In this talk, I will describe our initial studies evaluating the potential of human and chimpanzee organoid models to recapitulate features of normal brain development and to reveal evolutionary differences in developmental gene expression patterns. Ultimately, great ape organoid models, anchored in comparisons to available primary tissue, could be applied beyond studies of progenitor cell evolution to decode the genetic and developmental origin of recent changes in cellular organization, connectivity patterns, myelination, synaptic activity, and physiology that have been implicated in human cognition.
Bio: Alex Pollen is an Assistant Professor in the Department of Neurology at the University of California-San Francisco (UCSF). His lab combines advances in single cell genomics, genome engineering, and great ape cerebral organoids to study specialized features and vulnerabilities of the human brain. Alex received training in evolutionary genetics and neuroscience during his PhD studies with David Kingsley at Stanford University and training in stem cell biology and cortical development during his postdoctoral studies with Arnold Kriegstein at UCSF. As a postdoctoral fellow, Alex identified molecular specializations of outer radial glia that may contribute to the developmental and evolutionary expansion of the cerebral cortex. His research has been recognized by the NIH New Innovator Award, and awards from the Cajal Club, the Damon Runyon Research Foundation, and the Schmidt Futures Foundation.
"Human evolution and adaptation in Africa"
Abstract: Africa is thought to be the ancestral homeland of all modern human populations within the past 300,000 years. It is also a region of tremendous cultural, linguistic, climatic, and genetic diversity. Despite the important role that African populations have played in human history, they remain one of the most underrepresented groups in human genomics studies. A comprehensive knowledge of patterns of variation in African genomes is critical for a deeper understanding of human genomic diversity, the identification of functionally important genetic variation, the genetic basis of adaptation to diverse environments and diets, and the origins of modern humans. We have characterized genomic variation in thousands of ethnically and geographically diverse Africans in order to reconstruct human population history and local adaptation to variable environments. We identify ancient common ancestry among geographically diverse hunter-gatherer populations. In addition, we have identified candidate genes that play a role in adaptation to infectious disease, diet, high altitude, skin color, and stature.
Bio: Sarah Tishkoff is the David and Lyn Silfen University Professor in Genetics and Biology at the University of Pennsylvania, holding appointments in the School of Medicine and the School of Arts and Sciences. She is also Director of the Penn Center for Global Genomics and Health Equity. Dr. Tishkoff studies genomic and phenotypic variation in ethnically diverse Africans. Her research combines field work, laboratory research, and computational methods to examine African population history and how genetic variation can affect a wide range of traits – for example, why humans have different susceptibility to disease, how they metabolize drugs, and how they adapt through evolution. Dr. Tishkoff is a member of the National Academy of Sciences and a recipient of an NIH Pioneer Award, a David and Lucile Packard Career Award, a Burroughs/Wellcome Fund Career Award, an ASHG Curt Stern award, and a Penn Integrates Knowledge (PIK) endowed chair. She is a member of the Scientific Advisory Panel for the Packard Fellowships for Science and Engineering and the Board of Global Health at the National Academy of Sciences and is on the editorial boards at PLOS Genetics, Genome Research, G3 (Genes, Genomes, and Genetics). Her research is supported by grants from the National Institutes of Health and the National Science Foundation.
"Cell fate trajectories in cortical organoids in development and disease"
Abstract: Human induced pluripotent stem cell (iPSC)-derived organoids represent a tractable tool to investigate how human genetic diversity shapes brain development, and the underlying mechanisms by which gene regulatory elements drive cellular diversity in the brain. I will discuss the characterization of epigenomes and transcriptomes of human cortical organoids and, in parallel, isogenic human fetal brains. These studies allow to investigate how correlated networks of gene and enhancer modules exhibit dynamic changes in development, and how variation in enhancer elements in different individuals or during human evolution might affect the expression of their target genes.
Single cell transcriptome analyses reveal complex trajectories where progenitor cells in organoids diversify into different neuronal lineages and acquire dorso-ventral and medio-lateral identities. Furthermore, these trajectories are altered in developmental disorders. Hence, organoids promise to unravel genes and regulatory elements driving cell fate and brain patterning in normal and abnormal neurodevelopment.
Bio: Flora Vaccarino is the Harris Professor at the Child Study Center and Professor in the Department of Neuroscience at the Yale School of Medicine. She received her MD from the University of Padova in Italy and was a research fellow at NIMH and a clinical fellow in Psychiatry at the Yale School of Medicine. After four years of postdoctoral fellowship in developmental neuroscience and genetics at Yale, she was appointed to Assistant Professor, and subsequently Associate Professor and Professor at the Child Study Center and Department of Neuroscience at the Yale School of Medicine. Her interests are in mammalian brain development and particularly gene regulatory mechanisms that shape the earliest cell fate decisions in normal human brain development and neuropsychiatric diseases.
"Cell type classification and circuit mapping in the mouse brain"
Abstract: To understand brain function and how its dysfunction leads to brain diseases, it is essential to know about the cell type composition and connectivity in the brain. At the Allen Institute, we have built multiple platforms, including single-cell transcriptomics, single and multi-patching electrophysiology, 3D reconstruction of neuronal morphology, and brain-wide connectivity mapping, to characterize the transcriptomic, physiological, morphological, and connectional properties of different types of neurons in a standardized way, towards a taxonomy of cell types and a description of their wiring diagram for the mouse brain. Building such knowledge base lays the foundation for decoding brain circuit function.
Bio: Hongkui Zeng, Ph.D., is Executive Director of Structured Science in Allen Institute for Brain Science. She is leading the Structured Science Division to develop and operate high-throughput pipelines to generate large-scale, open-access datasets and tools to accelerate neuroscience discovery. Zeng received her Ph.D. in molecular and cell biology from Brandeis University, where she studied the molecular mechanisms of the circadian clock in fruit flies. Then as a postdoctoral fellow at Massachusetts Institute of Technology, she studied the molecular and synaptic mechanisms underlying hippocampus-dependent plasticity and learning. Since joining the Allen Institute, she has led several research programs, including the Transgenic Technology program, the Human Cortex Gene Survey project, the Allen Mouse Brain Connectivity Atlas project and the Cell Types program. She is also leading a BRAIN Initiative effort to create a Brain Cell Atlas in the mouse. She has broad scientific experience and a keen interest in using a combined molecular, anatomical and physiological approach to unravel mechanisms of brain circuitry and potential approaches for treating brain diseases. Her current research interests are in understanding neuronal diversity and connectivity in the visual cortical circuit and how different neuronal types work together to process and transform visual information. She has received many honors, including the 2016 AWIS Award for Scientific Advancement and the 2018 Gill Transformative Investigator Award.