8:30 - 9:15 a.m.

W. Malcolm Byrnes, Ernest E. Just: His Scientific Contributions and their Importance Today

Abstract: Ernest E. Just (1883-1941) was an African American embryologist who made significant contributions to biology despite a cultural milieu that was often hostile to his research efforts. Using a light microscope, he observed the wave of negativity that moves over the egg cell surface upon fertilization, and correlated the structural changes he saw with what is known as the fast block to polyspermy. He performed experiments to test the existing models of sperm-egg attraction and interaction. He investigated the effects of a range of conditions—hypertonic and hypotonic seawater, temperature, ultraviolet light, for example—on both normal development and parthenogenesis (egg activation in absence of sperm), and developed a set of indices of development that allowed him to predict with precision whether or not a given egg or embryo would develop normally. Through thirty years of work both in the United States at the Marine Biological Laboratory in Woods Hole, Massachusetts, and abroad in Italy, Germany and France, he came to see the cell surface and the structured layer below it as the key players in development, heredity and even evolution. He saw the egg cell and the embryo as living systems that respond to their environment. Just’s work and insights resonate with today’s integrated, systems view of biology, and with what is known as evolutionary developmental biology (Evo-Devo), especially its sub-category ecological developmental biology (Eco-Devo.) This talk first will outline E. E. Just’s scientific contributions, and then will show how each of the symposium’s scientific talks relates to those contributions. The goal will be to highlight the importance of Just’s work for biology today.

William A. Mohler, The Challenges and Benefits of High-Resolution Imaging of Intact Specimens

Abstract: As E. E. Just wrote, “Only in the egg and its development can we hope to trace to its source the pattern of structure, and to resolve into its motif the harmonious behavior which characterizes the many-celled animals.” One of the various beauties of oviparous development is that biologists can hope to witness all of the events that occur as the egg transforms itself into a many-celled animal. Entire genomes have been recently catalogued for many species, and molecular biology and optical engineering have advanced, in a mere seventy years, to a point that Dr. Just likely never dreamed. It is now, therefore, conceivable to specifically label and observe each of the molecules that makes up the living whole, to witness their action throughout the course of embryogenesis, and to fit this knowledge of the smallest components of the machine into a holistic model of how the organism functions as an irreducible living entity. In the 21^st century we may realistically expect to satisfy both the yearnings of an organicist like Just and the reductionist ideals that have grown to predominate in biology since his time. This talk will introduce some of the technologies that allow today’s biologists to envision a state of knowledge that E.E. Just had in mind nearly a century ago.

10:15 - 11:00 a.m.

Malgorzata Kloc, Emerging Novel Functions of RNAs, and Binary Phenotype

Abstract: RNAs function in a wide variety of processes in the nucleus and cytoplasm, including regulation of translation, RNA editing, and gene regulation. Additionally, a class of localized RNAs found in specific regions of the cell or embryo play functional roles in mitotic spindle assembly, cell polarization, and development. It was recently found that structural RNAs are associated with mitotic spindle and asters: these RNAs control the dynamic of microtubules and play a direct, translation-independent role in mitotic spindle apparatus assembly in Xenopus leavis egg extracts and in human HeLa cells. Recently, the structural RNAs were also found to function in maintaining the integrity of the cyotkeratin and actin cytoskeleton in frog (Xenopus) oocytes. These studies point to completely novel and unexpected functions of RNAs and suggest that, at least in some cases, the normal cell or embryo phenotype is in fact binary, i.e., it depends not only on the function of the protein but also on the autonomous function of its mRNA. Since the assumption is and always has been that the only relevant function of mRNA is to make a protein, and thus, the effect of removing mRNA equals the effect of removing its protein, these new findings may require us to rethink and re-evaluate some of the loss-of-function data collected through the years. They will open new frontiers in the study of RNA function.

11:00 - 11:45 a.m.

Paul Wassarman, Mammalian Fertilization: Molecular Profile of a Sperm Receptor

Abstract: An early step in fertilization among mammals is species-restricted binding of acrosome-intact sperm to the zona pellucida (ZP), the egg's thick extracellular coat. Sperm bind to the ZP of unfertilized eggs, but not to the ZP of fertilized eggs or embryos. Shortly after binding to the unfertilized egg ZP, sperm undergo the acrosome reaction (cellular exocytosis), penetrate the ZP, and fuse with the egg's plasma membrane to form a zygote. Three glycoproteins, named ZP1, 2, and 3, constitute the mouse egg's ZP and these glycoproteins participate directly in the process of fertilization. For example, sperm exposed to purified, unfertilized egg ZP3 at nanomolar concentrations are inhibited from binding to eggs and undergo the acrosome reaction in vitro; purified ZP1 and ZP2 have no effect on sperm binding or induction of the acrosome reaction. Furthermore, ZP3 purified from fertilized eggs or embryos has no effect on sperm binding and is unable to induce the acrosome reaction. Female mice that are homozygous nulls for the ZP3 gene are infertile and their eggs lack a ZP. These and several other properties of ZP3 strongly suggest that it is a receptor for sperm and an inducer of the acrosome reaction. Mapping of the ZP3 combining-site for sperm suggests that it is located near the carboxy-terminus of the polypeptide, in a region encoded by exon-7 of the ZP3 gene. For example, when ZP3 exon-7 is fused to the Fc fragment of human immunoglobulin and sperm exposed to the fusion protein, the sperm are inhibited from binding to eggs, but do not undergo the acrosome reaction in vitro.  These, as well as other aspects of ZP3 and mammalian fertilization will be presented.

11:45 a.m. - 12:30 p.m.

Gary Wessel, Cell Surface Changes in the Egg at Fertilization

Abstract: Within the first 60 seconds of fertilization, the egg transforms the mechanical and molecular properties of its cell surface from one of attracting sperm to one of blocking subsequent sperm. The sea urchin egg is marked in this behavior, and was a major focus of Just's work. We now know that the fertilization envelope is composed of six major proteins derived from five transcripts. The vast majority of the envelope mass is from proteins adept at interacting with each other through repeated protein interaction domains: CUB (the rendezvins) and LDLr (SFE1, SFE9, proteoliaisin) motifs. Each is present in the major envelope proteins in tandem arrays of several to dozens, respectively.  As the envelope forms, these structural protein interactions are modified by enzymatic cross-linking activities, dityrosine and transamidations, which stabilize the matrix against chemical and mechanical stress. Two other enzymes are also essential in this chronolog of envelope activities. One is a serine protease derived from the cortical granules. It cleaves p160, another CUB containing protein that appears to link the nascent extracellular matrix of the egg, the vitelline layer, to the plasma membrane. Cleavage of p160 enables the envelope to lift and separate from the plasma membrane. Surprisingly, the protease activity is markedly specific; of the hundreds of proteins on the cell surface, no more than approximately 20-25 are cleaved by the protease. Finally, an NADPH-dependent dual oxidase is activated by calcium in the cytoplasm to generate the peroxide for peroxidase-mediated cross-linking activities. This oxidase activity was originally attributed to mitochondrial activity for the respiratory burst, a term coined by Otto Warburg while Just was still working in Woods Hole. If this chronology of egg cell surface activities is sufficiently precise, the harmony of development is possible. Or better, in the words of Just, “The most minute space-time organization of the living system makes the instrument on whose strings play the processes by action and interaction. By experiment we here slightly exaggerate, there lightly fret the tones out of which the harmony of the living state arises.” (Just, The Biology of the Cell Surface, pg. 30, 1939.)

1:00 - 1:15 p.m.

Orlando L. Taylor, The Howard University Science Legacy

Abstract: There were a number of scientists at Howard who helped to build a reputation in the physical and biological sciences that led to the awarding of the first doctoral degree (in chemistry) at the university. People like Ernest Just in Biology, Percy Julian in Chemistry, Montague Cobb in Anatomy and others helped to build a research infrastructure in which PhD programs could be mapped. Similarly, in the College of Medicine, strong programs had already been established to undergird medical education. Thus, there was a biomedical science faculty already in place to teach medical students, and many were doing research. So the presence of a medical school at Howard and the scientific underpinnings that were already in place elsewhere on campus made the natural sciences a good area in which to launch PhD studies. Fifty years after awarding its first degree in 1958, Howard University now awards upwards of 100 PhDs per year. We continue to expand our vision and aspirations, seek to maintain and strengthen our existing programs, and build upon the legacy we have established. 

1:15 - 2:00 p.m.

Kenneth R. Manning, E. E. Just and African Americans in Scence and Medicine

Abstract: The talk will cast the life and work of E. E. Just onto the canvas of the last twenty-five years.  It will address the progress of African Americans in science since the publication of Black Apollo of  Science in 1983, and specifically, in the most recent so-called Age of Obama.

2:00 - 2:45 p.m.

Mariusz Nowacki, An RNA-Mediated Epigenetic Mechanism for Inheritance of Acquired Mutations

Abstract: RNA, normally thought of as a conduit in gene expression, has a novel mode of action in ciliates, where maternal RNA templates provide both an organizing guide for DNA rearrangements and a template that can transmit spontaneous point substitutions that may arise during somatic growth to the next generation (Nowacki et al. (2008) Nature 451:153-8). This opportunity for RNA-guided DNA repair is profound in its regulation of global DNA rearrangements in Oxytricha, involving loss of 95% of its germline genome, through a process that severely fragments its chromosomes and then sorts and reorders the hundreds of thousands of pieces remaining. Information for reordering comes from transiently-expressed maternal RNAs. Furthermore, the occasional transfer of point mutations in these RNA templates to the rearranged molecules provides a mechanism for stable inheritance of acquired, spontaneous somatic mutations (in either DNA sequence or alternative splicing pattern) without altering the germline genome. This mechanism for inheritance beyond the conventional DNA genome can epigenetically transfer information across multiple generations, hinting at the power of RNA molecules to shape genome information. The evolutionary consequences of a viable mechanism in ciliates to transmit acquired characters may contribute to their cosmopolitan success, as well as high substitution rates in somatic sequence comparisons.

2:45 - 3:30 p.m.

Rachel Brewster, The Brawn behind Brain Cells: Mechanisms of Neural Tube Morphogenesis

Abstract: The neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system, is shaped during a series of morphogenetic movements commonly known as neurulation. Knowledge of the mechanisms of neurulation are essential, given the high incidence of human neural tube birth defects, in particular in posterior regions of the embryo. In order to condense into a neural cord, posterior neural cells must first converge toward the dorsal midline of the embryo. Once the cells have condensed into a neural cord, they undergo a mesenchymal-to-epithelial transition. Surprisingly little is known about how these events are orchestrated. The Brewster laboratory uses the zebrafish as a model system to investigate mechanisms of posterior neurulation. Using time lapse imaging and single cell labeling, we have found that neural cell condensation involves a number of discrete behaviors, such as protrusive activity, that allows for directed migration, and cell-cell adhesion. We have identified several key molecules that regulate these behaviors. The role of the cell adhesion molecule N-cadherin, the cell polarity genes aPKC and par3, and linguini, a novel gene identified in a forward genetic screen, will be discussed.

3:30 - 4:15 p.m.

Stuart A. Newman, Developmental Systems as Excitable Media: Variations on a Justian Theme

Abstract: E. E. Just advocated a non-reductionist approach to biology in which genes, rather than directing development, are components of complex dynamical systems, phenotype emerges through the organism’s interaction with its environment, and development and evolution are understandable only in relation to one another. This talk will explore Just’s theme by considering the role played by a core set of “dynamical patterning modules” (DPMs) in the origination, development and evolution of the Metazoa (multicellular animals). DPMs consist of the products of a subset of what has come to be known as the “developmental-genetic toolkit” in association with specific physical processes or effects that each (or groups) of these molecules mobilize in the context of multicellularity. The physical effects include cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on “lateral inhibition,” and global coordination of cellular states. I will describe how the major features of modern-day developmental mechanism can be understood in terms of a small number of DPMs, which thereby constitute a “pattern language” for metazoan form. Most importantly, this new framework provides an understanding of how the multicellular organisms of the late Precambrian-early Cambrian could have rapidly diversified into the prototypes of the animal phyla during the “Cambrian explosion” using a common molecular toolkit in conjunction with physics-based morphological plasticity.

4:30 - 5:15 p.m.

Sonia Sultan, Studying Development in Context: The Eco-Devo Approach

Abstract: Ecological development is the study of development in ecological context. It addresses the mechanisms and outcomes of individual phenotypic expression in response to the varying environmental conditions that organisms encounter in the real world. In a neo-Darwinian model, the phenotype is seen as the determined outcome of internal, genetic information; environmental conditions are irrelevant except as they allow normal development to occur. In contrast, the Eco-Devo approach arises from a “norm of reaction” or plasticity model, in which a genotype may express one of several possible phenotypes, depending on its environment. In this view, the individual’s particular physical and biotic circumstances are important influences on development. Accordingly, in place of the putatively neutral or “control” conditions of traditional developmental studies, Eco-Devo studies seek to incorporate meaningful environmental variation into their designs. An individual’s developmental repertoire for traits of interest can be determined by raising genetic replicates in a range of environments that is based on the actual (or potential) conditions that species may experience. These expression patterns are trait- and environment-specific, and may vary at the genotype, population, and species levels. Accordingly, plasticity patterns can be understood as evolving traits. Environmentally conditioned phenotypic outcomes can be either adaptive adjustments that maintain growth and reproduction in an environment, or maladaptive changes that reduce fitness in that environment. Both aspects of eco-devo variation affect the ecological distribution and evolutionary future of natural populations. Information on environmental response patterns is particularly critical at present, as we aim to understand (and perhaps prevent) some of the phenotypic impacts of a host of anthropogenic environmental changes, from toxic agrochemicals and other contaminants to global climate and atmospheric change.

5:15 - 6:00 p.m.

Gerd B. Müller, The Environment-Development Relation and the Biologische Versuchsanstalt in Vienna

Abstract: In his studies of the egg cell, Ernest Everett Just emphasized the role of the environmental conditions under which fertilization and the processes of development take place. In many institutions where he had worked, such as the marine biological laboratories at Woods Hole, Roscoff, and Naples, the rise of experimental embryology and its focus on the internal mechanisms of animal development made Just’s emphasis on external conditions and the determinative role of the natural setting seem somewhat unorthodox. By contrast, in the field of evolutionary biology, during the same period of the early 20^th century, there existed a strong interest in the influences of the environment on evolutionary processes. In Austria, a forefront institute of experimental research, the “Biologische Versuchsanstalt” at Vienna, also called the “Vivarium”, was entirely designed and equipped to explore the effects of environmental conditions on organismal development and evolution. The Versuchsanstalt also pioneered quantitative methods and mathematical modeling, helping pave the way for theoretical abstraction in biology. Thus the modern fields of Eco-Devo and Theoretical Biology have important roots in the Vienna Vivarium. My lecture will present some selected topics of the research program of this once famous institution and set them in relation to Just’s ideas.