MOLECULAR B IOS CIENCES MINICOURS ES S P RING 2014 DAVID AXELROD: C ANCER G ENES AND C ELLS 16:695:621 De s c rip tio n : After successfully completing this course, students will have gained knowledge of cancer as the consequence of abnormal processes at the genetic, molecular, and cellular levels. They will have learned how some of that knowledge has been obtained and will appreciate what is not yet known. They will be able to critically evaluate published experimental cancer literature, to identify fruitful new avenues of research, and to propose new experiments to learn more about these processes. They will have had experience in communicating their ideas effectively in oral and written formats. S IOBAIN DUFFY: E VOLUTION OF E MERGING VIRUS ES 16:695:622 De s c rip tio n : Evolution is the unifying principle of all biological sciences, including molecular biology. The mechanisms by which enzymes, genes and non-coding regions of genomes have evolved are important to study, and molecular evolution is a mature and robust field. This course will expose students to the principles of evolution, with a heavy emphasis on molecular evolution, using fast-evolving viruses as the example. This course will also therefore give students a broad background in the diverse RNA and single-stranded DNA viruses that frequently emerge in novel hosts. After successfully completing this course, students will have an increased understanding of molecular evolution, its applications in the literature, and the unique features of viral genomic architectures and ecology that influence their evolution. The presentations, class discussion and exam will emphasize unpacking figures from published papers, and students will learn how better to interpret and present research figures. S AM G U & MIKEL ZARATIEGUI: NONCODING R EGULATORY RNA 16:695:623 De s c rip tio n : The ability of non-coding RNA to trigger specific chromatin responses and long-term epigenetic effects has been found in eukaryotic organisms from yeast to humans. Research in this area has profound implications for understanding genome-environment interaction and inheritance of expression states relevant to human development and disease. This course will cover some of the key mechanisms in the topic. WILMA O LSON:G ENETIC S YSTEMS AND S TRUCTURES 16:695:624 De s c rip tio n : The packaging of genomes is complicated by the necessity of maintaining the accessibility of DNA for genetic processing. The binding of various proteins to DNA plays an important role in reading and compacting the genome. This short course will address the interplay between local and large-scale biomolecular structure and function, including the contributions of regulatory and architectural proteins to the organization of DNA and the control of genetic expression. Students successfully completing this course will have gained a working knowledge of the three-dimensional structures and dynamics of representative protein-DNA systems and a new appreciation of the large-scale macromolecular organization of DNA and chromatin gleaned from genetic and single-molecule experiments. In addition, the skills required for critical evaluation of the literature and presentation of scientific data will be honed. WENWEI HU AND ZHAOHUI F ENG : P 53 16:695:625 De s c rip tio n : p53, which was discovered in 1979, is the most frequently mutated tumor suppressor gene in human cancer. In the past 30 years, the function of p53 has been the subject of intensive research, and new revelations about p53 function have not declined with age. p53 functions as a node in numerous signaling pathways to regulate many important biological activities. In addition to its pivotal role in tumor suppression, recent studies have shown that p53 is critically involved in many other physiological and pathological processes. Furthermore, it is clear that p53 is therapeutically important and many approaches are being taken to reconstitute its function in tumors. In this course, we will introduce some of our current understanding of p53 function by giving 2 lectures and using 6 examples from the current literature. Students that successfully complete this course will gain a rich knowledge of tumor suppressor p53 and its signaling pathway in cancer and other diseases. In addition, students will learn the skills to critically evaluate the literature and scientifically present a paper. DAVID AXELROD: C ANCER AND C LINICAL O NCOLOGY 16:695:626 De s c rip tio n : After successfully completing this course, students will have gained knowledge of some of the properties of cancer cells and tissues that have a clinical impact. They will have learned how that knowledge has been obtained and translated to improve diagnosis, prognosis and therapy of cancer patients. They will also appreciate what has not yet been achieved. They will be able to critically evaluate published cancer literature, to identify fruitful new avenues of research, and to propose new experiments that could provide experimental results that could be translated into patient benefit. They will have had experience in communicating their ideas effectively in oral and written formats. KIRAN MADURA: UNDERSTANDING THE UBIQUITIN/PROTEAS OME SYSTEM AND ITS INVOLVEMENT IN DISEASE 16:695:627 De s c rip tio n : The degradation of cellular proteins is essential for many biochemical mechanisms including DNA replication, transcription and repair, cell cycle control, response to environmental stresses, and the elimination of damaged proteins. The primary mechanism of intracellular protein turnover involves the ubiquitin/proteasome system (UPS). In contrast to most scientific disciplines, this is a new area of inquiry (the basic biochemistry was unraveled in the early 1990's) and earned three scientists the Nobel Prize in Chemistry in 2004. The biological and clinical significance of the UPS has emerged more recently (during the past 10-15 years). It is now clear that a failure in the ubiquitin/proteasome system contributes significantly to many maladaptive and disease conditions, including cancers which have increased UPS activity, and neurodegenerative conditions that are associated with reduced activity. The focus of this course is two-fold. Several lectures will begin by characterizing the mechanism of intracellular protein degradation. These discussions will refer to seminal papers in the field, and will also consider key methodological approaches that were used to address scientific questions. The course will conclude with a consideration of the disease implications. The proteasome is a multi catalytic protease in the UPS, and is a target for inhibition in the treatment of multiple myeloma and other diseases. Several additional cancers that might be treated with proteasome inhibitors are under investigation, demonstrating the relevance of the UPS in clinical therapy. MICHAEL VERZI & KELVIN KWAN: P LURIPOTENT AND S OMATIC S TEM C ELLS 16:695:628 De s c rip tio n : Somatic and pluripotent stem cells are likely the most important source for healthy tissue regeneration and cancer. This course will engage in discussions and lectures to develop concepts and hypotheses surrounding the identity and functions of stem cells. This will be accomplished using intestinal and pluripotent stem cells as model cellular systems. After successfully completing this course, students should be able to design approaches to identify and functionally characterize somatic stem cells. They should be able to develop approaches to use stem cells in regenerative medicine or as targets for cancer therapy and prevention. ANDY S INGSON: G ENETICS AND C ELL B IOLOGY OF F ERTILIZATION 16:695:629 De s c rip tio n : The union of sperm and egg is required for the propagation of all sexually reproducing species. The underlying molecular mechanisms of fertilization are also paradigms for other important cell-cell interactions during development. After successfully completing this course, students will have gained a broad perspective of the field of fertilization that will include a historical point of view as well as an understanding of the current challenges in reproductive biology. DEANNE TAYLOR: INTRODUCTION TO S YS TEMS B IOLOGY 16:695:630 De s c rip tio n : Systems biology is a field that aims to provide an integrative, system-level understanding of biology through the modeling of experimental data. The course covers an introduction to specific applications of systems-level analysis of genomic and genetic data, with supportive background to the primary literature assignments. Topics covered are in the analysis of interaction networks, regulatory networks and modeling of metabolic and physiological systems. Students will have hands-on experience with analysis of biological networks with assignments that walk them through data analysis sourced from primary literature. After successfully completing this course, students will have exposure to algorithmic methods and publicly available tools for analysis and modeling of complex biological networks, including strengths and weaknesses of each approach. They will be aware of major projects underway in functional genomics and genetics and what data and resources are available for systems-level analysis. DAVID MARGOLIS & KELVIN KWAN: NEURAL C IRCUIT MICROS COP Y 16:695:631 De s c rip tio n : Lectures will be designed to discuss cutting-edge techniques used to map neuronal circuits. The lectures will revolve around how to use microscopy techniques to address challenges and questions facing the field. The assigned reading will be seminal work that answered these challenges/questions. The class begins with lectures on the microscopy technique followed by discussion of the assigned reading and culminates by introducing the next big question/challenge and assigning the paper that addresses it. After successfully completing this course, students should be able to design approaches to map, identify and characterize neuronal circuits. Students will come away with an understanding of how to use various powerful microscopy techniques to answer key questions in neuroscience. B EATRICE HAIMOVICH: TOLL-LIKE R ECEP TORS IN HEALTH AND DIS EAS E 16:695:632 De s c rip tio n : Toll-like receptors (TLRs) and inflammasomes are protein complexes that become activated in response to a variety of pathogen-derived and host-cell derived noxious insults. In this course we will examine mechanisms by which TLRs and inflammasomes regulate inflammatory responses, and link these processes to host homeostasis as well as human diseases. After successfully completing this course, students will have a working knowledge of TLRs and how inflammasomes function in host defense. The classes will emphasize student-led critical evaluation and discussion of current literature. J IM MILLONIG & E MANUEL DICICCO -B LOOM: NEURODEVELOP MENTAL DISORDERS 16:695:634 The goal of this course is to teach the molecular, developmental and genetic bases of autism spectrum disorder and related Mendelian diseases (e.g., Fragile X, Rett, Tuberous Sclerosis and Timothy syndromes). Each week seminal papers will be discussed by Emanuel DiCicco-Bloom MD, a developmental neurobiologist and child neurologist, and Jim Millonig PhD, a molecular geneticist. Papers will be selected that have led to greater understanding of the underlying pathology and the development of new treatments. A variety of cutting edge techniques such as immortalized pluripotent stem cells (iPSCs) will be introduced and the positives and negatives of these approaches will be discussed. Each week one disease will be examined with Dr Millonig leading the molecular genetic aspects while Dr DiCicco-Bloom will focus on the developmental studies. By the end of this minicourse students should have a greater understanding of these diseases, how scientific advances have led to the development of new treatments and the challenges facing the generation of new therapies. R ANDY MC KINNON: R EGENERATIVE MEDICINE - S TEM C ELL THERAP Y 16:695:635 De s c rip tio n : The 2012 Nobel Prize in Medicine was awarded to Drs. Gurdon (UK) and Yamanaka (Japan) for cellular reprogramming. This course will consider the biological rationale for using reprogrammed cells in molecular medicine, then dive into the details of what this technology is and why it holds so much promise. The emphasis will be on molecular mechanisms of cell lineage determination. After successfully completing this course, students will gain a working knowledge of the current status of stem cells (biology, engineering, reprogramming, and therapeutics). A primary focus will be to give students the skill sets necessary to critically read and evaluate the biomedical literature, and to gain experience in presenting scientific data. MIKE HAMP S EY: C ANCER C ELL METABOLIS M 16:695:636 De s c rip tio n : A characteristic of all cancer cells, including well-oxygenated tumors, is the “Warburg Effect,” defined as the massive uptake of glucose and its metabolism by “aerobic glycolysis,” rather than by the more energy efficient process of respiration. The Warburg Effect is the basis of one of most definitive cancer diagnostics: PET scan of tissues that take up radio labeled 19F-2-deoxyglucose, a non-matabolizable glucose analog. Despite having first been reported in 1923, the Warburg Effect remains unexplained. This course will focus on metabolic pathways that have gone awry in cancer cells. The format will include presentation and critical discussion of recent results from the literature. Emphasis will be placed on what we don’t know about cancer cell metabolism, in the context of established metabolic pathways. The resurgence of interest in the Warburg Effect, and the new research opportunities that this affords, will be a major theme.