Biology Department

Abstract: How epigenetic memory is passed from parents to offspring and through development are areas of intense investigation. In C. elegans, both sperm and oocytes transmit a memory of gene repression and gene expression to embryos in the form of modified histones, methylated H3K27 for repression and methylated H3K36 for expression. During DNA replication modified histones are passed to daughter chromatids and can provide chromatin memory for a few cell divisions. Histone-modifying enzymes (PRC2 for repression and MES-4 for expression) are needed to replenish histone modifications and provide long-term chromatin memory. Such memory is required for development of the next generation of germ cells.

General Theme: Chemical Interactions between Organisms. Specific research focus: discovery and characterization of venom components, identification of their molecular targets, and an exploration of potential biomedical applications in venomous marine snails.

Georgina conducts and directs research into the transfer and persistence of DNA and other trace evidence. She is particularly interested in the indirect transfer of DNA and how this affects the evaluation of trace DNA in casework. She collaborates with DNA experts from across the world to progress and raise the profile of this important area of research. Georgina still consults in casework to ensure that her research addresses the critical issues faced in forensic science practice, and also lectures on the Crime and Forensic Science MSc programme.

Join students from Biology, Chemistry, Math, Physics, and Psychology as they present the results of their summer research and projects.

Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye.

Reed College offers many resources to help students be successful both at Reed and beyond. Come meet some of the people from around campus who can help out and learn about what they can do for you!

Circuits underlying motor patterns of closely related species provide an ideal framework in which to study how evolutionary forces shape behavioral variation. Male African clawed frogs produce a species-specific advertisement call to attract female mates. Xenopus laevis is the most well-studied species in terms of its vocal behavior and underlying anatomy and physiology. The clade that includes X. laevis also includes 3 other species that diverged ~8.5 million years ago. All 4 of these species produce advertisement calls that include fast trill­­­s – trains of fast rate (~60 Hz) sound pulses. However, their calls differ substantially between species in measures of trill duration and period. I examined the premotor circuit underlying vocal patterning in three of these species: X. laevis, X. petersii, and X. victorianus. I used extracellular recordings to find that a premotor nucleus, DTAM, which is part of the vocal central pattern generator, is the likely source of species-variation of vocal patterns. Species-specific trill duration and period are intrinsic to the region of the hindbrain that includes DTAM. Next, I used blind whole-cell patch recordings in DTAM of X. laevis and X. petersii to examine the cells that encode trill duration and period. I identified homologous populations of premotor vocal cells in both species that code for trill duration and period in a species-specific manner. Together, these results support an autonomous role of the DTAM circuit for generation of species variation in call duration and period.

Many motor behaviors are generated by circuits called central pattern generators (CPGs) that can produce rhythmic motor patterns without patterned input. In a canonical view, vertebrate motor systems operate in a top-down manner: rhythmic activity produced by the CPG leads to activation of motor neurons, which in turn activate muscles. My group studies the vocal CPG of the frog, Xenopus laevis, as a means of identifying fundamental principles that govern motor production. In contrast to the top-down view of a “textbook” motor circuit, we found evidence that motor neurons may be essential players in the production of vocal patterns. Specifically, we have discovered that motor neurons project to and modify the activity of vocal CPG neurons. When this feedback projection is blocked, the vocal CPG becomes incapable of generating vocal patterns. These results indicate a unique circuit property in which motor neurons are essential components of the CPG, not mere relays between the CPG and muscles. This work supports the notion that motor neuron involvement in vertebrate CPG function may be the rule rather than the exception.

Cells contain structural elements, collectively referred to as the cytoskeleton. The cytoskeleton is more dynamic than its name implies. A dynamic cytoskeleton is critical for many processes, including cell polarity, division, and motility. In early development, cell polarity leads to establishment of the major body axes (e.g., where the head and tail go). We are studying two proteins that stimulate formation of actin filaments, the nucleators Spire (Spir) and Cappuccino (Capu), and are essential to polarity establishment during early development. Spir and Capu collaborate to build an actin mesh that traverses the Drosophila oocyte throughout mid-oogenesis. The presence of the mesh and its timely removal are both critical to polarity establishment. In the Quinlan lab, we combine the power of Drosophila genetics with physical biochemistry and cell biology. Our goal is to develop a mechanistic understanding of Spir and Capu, advancing our knowledge of the cytoskeleton and how it is controlled. This conserved pair of proteins co-exists in other polar cells, including neurons and epithelial cells in mammals. Thus we anticipate that what we learn about Spir and Capu in Drosophila oogenesis will be applicable to our understanding of fundamental biological principals and disease in all animals.

Sexual selection, more so than natural selection, is posited as the major cause of sex differences. Dr. Cooper's research shows the ecological correlations between solar radiation levels and sexual dimorphism in body color of a Hawaiian damselfly.

The germ theory of disease was a landmark moment in human progress because it catalyzed progress that greatly reduced mortality from infectious diseases. However, the germ theory left unanswered two major questions that have preoccupied scientists for the past century: 1) why are some microbes pathogenic and others not? 2) why are some hosts susceptible and others not? To these question can be added the deeper question: how does the capacity for virulence emerge in some microbes? For microbes acquired from other hosts virulence, which includes many common pathogenic microbes, disease often results from host-microbe interactions that perturb host homeostasis. However, for the set of pathogenic microbes that are acquired directly from the environment, the origin of virulence is less clear, since those microbes have no need for animal virulence for their survival. Among the best candidates to study these problems are pathogenic fungi, which provide clear example of pathogenic microbes acquired from other hosts and directly from the environment. Studies with the fungus Cryptococcus neoformans have provided insight in how virulence can emerge in the environment through pressures that have no relation to the final host. C. neoformans is often found in the same environmental niches as amoeba, and fungal-amoeba interactions have been proposed to select for traits that also allow it to survive in mammalian hosts, in a process that has been called accidental virulence. A comparison of the interaction between amoeba and mammalian phagocytic cells reveals remarkable similarities in intracellular survival strategy despite the enormous phylogenetic distances for these two cellular hosts. Many of the virulence factors that are needed for C. neoformans virulence in mammals are also needed for survival against amoeba predation. The experience with C. neoformans has now been corroborated for several other pathogenic fungi. The environmental predatory selection hypothesis can also explain the non-specific nature of environmental fungal pathogens. Furthermore consideration of host susceptibility to fungal pathogens provides a fertile ground for re-thinking evolutionary processes including great mammalian radiation and the end of the age of reptiles after the events at the Cretaceous-Tertiary boundary.

Learn about upcoming events in the department as well as opportunities for summer research, internships & fellowships.

Details will be announced to community members prior to talk.

Do you think you might go to grad school or med school? Whether you are a freshman or a senior Janis and Sarah will help you decide which option might be right for you and how to prepare for the application process.

Details will be announced to community members prior to talk.

Details will be announced to community members prior to talk.

A “disease outcome” can refer to a behavior, event, state, or condition for some aspect of a patient’s health status. For example, a behavior may correspond to drug efficacy and treatment responsiveness, while an event may correspond to patient survival. In tumors, one way to evaluate behavior is by monitoring tumor angiogenesis (formation of new blood vessels necessary for tumor to nourish itself and sustain its existence) and its vasculature permeability through dynamic imaging, in which a series of images at different time instances are acquired for a specific tumor site after injecting a contrast agent to examine tumor vasculature patterns based on accumulation and washout of the contrast agent. Observing this activity over time can reflect the tumor drug responsiveness and efficacy of the treatment plan. As for evaluating patient survival, accurate estimation of patient prognosis fosters the new era of personalized medicine through health planning, treatment strategies, and drugs customized to the individual patient rather than being chosen based on their average effect on broader population cohorts. Incorporating the underlying biology in designing the survival prediction models can provide biologically relevant insights rather than relying only on the statistical significance of the outputs. In this talk, I present my previous work on characterizing tumor angiogenesis and on designing biologically informed and integrative approaches for survival analysis by considering the integration of a set of interacting multi-platform molecular data and the underlying biology.

In his seminal book On the Origin of Species, Charles Darwin’s proposed his revolutionary theory of evolution by natural selection. Throughout his career, however, the answers to many questions remained elusive. Building on the work of Darwin and the scores of scientists that followed him, we present work in our lab that addresses two important questions that Darwin never answered. The first study explores how new species arise, a process that Darwin called the “mystery of mysteries.” Using populations of island birds that are currently evolving into new species, this study combines field experiments with genomic techniques to explore the origin of new species. The second study explores the evolution of cooperation, a question that puzzled Darwin given that in some insect societies individuals sacrifice their own ability to reproduce to help a single individual in the colony. Using social wasps, this work combines field experiments with genetic and neuroanatomical techniques to understand how and why individuals cooperate given the benefits of cheating.

Despite the continuous effort to end the spread of infectious diseases, they remain the leading cause of death worldwide. The profound success of pathogens in causing disease depends on their ability to successfully utilize the host’s cellular machinery for their own advantage to avert its immune system. Understanding these pathways or processes essential for the life cycle of these pathogens is crucial, as it represents potential targets for new drug strategies. The research focus in my lab is on M. tuberculosis as well as HIV and viruses from the family Flaviviridae, which includes zika and dengue virus. We are interested in identifying and characterizing the host factors that are used by pathogens to secure invasion, persistence and propagation. We are especially interested in studying the role of cellular lipids in bacterial and/or viral pathogenesis and their significance on innate and adaptive immunity. We employ genome-wide genetic screens, various lipidomic analysis techniques and state-of-the art microscopy and other biochemical tools to define the pathogenesis of these microbes. Additionally, we aim to apply novel strategies such as the use of Alpaca-derived single-domain antibodies/nanobodies not only to unravel the intricate relationships of these pathogens with the host but also to use it as a diagnostic and therapeutics tools.

Computational analysis of protein networks is pervasive in systems biology. However, the problem of using such networks to predict when signaling pathways may crosstalk has received very little attention. Existing computational methods that may be applied to discover such pathway pairs rely on simple overlap statistics between the proteins and interactions in the two pathways. We present XTalk, the first path-based approach for identifying pairs of pathways that may crosstalk. XTalk starts from the biological definition of crosstalk: when the stimulation of one pathway's receptors triggers a response downstream of the transcription factors of a different pathway. XTalk uses an efficient dynamic program to compute the exact statistical significance of the average length of multiple short paths that connect receptors in one pathway to the transcription factors in another. By design, XTalk reports the precise network of interactions and mechanisms that support the identified crosstalk. To evaluate XTalk, we manually curated the first ever gold standard dataset of 132 crosstalking pathway pairs and a set of 140 pairs that did not crosstalk. XTalk achieved an area under the ROC curve (AUC) of 0.65, a 12% improvement over the closest competing approach. The AUC varied with the pathway, suggesting that crosstalk should be evaluated on a pathway-by-pathway level. To conclude, we discuss the difficulties in creating an accurate gold standard and evaluating crosstalk algorithms and propose ideas for addressing these challenges.

Phytoplankton blooms are major events in aquatic ecosystems that have important ecological and biogeochemical consequences. Initiation, development, and termination of blooms are governed by complex predator-prey interactions and physically-driven variations in light, nutrient, and temperature conditions. Understanding these dependencies is fundamental to assessing future change in bloom frequency, duration, and magnitude and represents a fundamental challenge in global change biology. In recent years, advanced field and remote sensing technologies have challenged traditional interpretations of blooms and yielded new insights on processes controlling annual cycles in phytoplankton biomass. This seminar will highlight some of these new developments, contrast them with historical interpretations, and look forward to future directions for research.

Details will be announced to community members prior to talk.

Details will be announced to community members prior to talk.

Brief lectures presented by thesis students about their thesis projects

Telomeres are repetitive DNA sequences at chromosomes ends, that protect chromosomes ends. Every time a cell divides telomeres shorten by a small amount. This shortening is counter balanced by the action of telomerase, which adds telomere DNA repeats and elongates telomeres. Telomeres are thus not unique size but rather are maintained about an equilibrium length. If telomeres become too short they induce DNA Damage and cause cell death. Cancer cells increase telomerase to maintain telomere length to allow for continuous growth, conversely a failure to maintain telomeres in adult stem cells causes loss of tissue renewal. Short telomeres cause inherited Telomere Syndromes in humans, a group of diseases, which include pulmonary fibrosis, emphysema, bone marrow failure, liver and other disease. We seek to understand the mechanisms that establish and regulate the telomere length equilibrium to establish approaches to intervene in cancer and age-related degenerative disease.

Dr. Kwan's lab studies the cellular and molecular mechanisms underlying tissue morphogenesis: the process by which a group of cells achieves its proper cellular organization and shape. Using the vertebrate eye as a model, we want to understand how the cells that comprise the vertebrate optic cup – neural retina, retinal pigmented epithelium, and lens – form the stereotyped structure that is critical for visual function. Developmental defects in eye morphogenesis represent a common cause of serious visual impairment in newborns.