Course Organizers (2008-2009)
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| 1 - GENE EXPRESSION
How genes command – an overview of eukaryotic gene control 6-18 October 2008 Organizer: João Ferreira, FML/IMM AIMS To provide a broad overview on how genes determine cellular and tissue activities. Students should be able to understand with sufficient mechanistic detail how gene activity impacts protein-based machineries to accomplish function. Also, how gene expression programs operate via regulation at the transcriptional and post-transcriptional levels. Finally, the role of epigenetic modulation of gene expression must be understood. Together, these concepts shall provide the basis for an informed appraisal of the impact of modern biology in medicine (prevention, diagnosis and therapy). This module shall also provide the background information on which subsequent modules are predicated. General topics Transcriptional control of gene expression Post-transcriptional gene control
Faculty
SCHEDULE: Week 1: a. Days 1-3: General Topics b. Days 4-5: Specific topic – Gene expression programs Week 2
a. Days 1-2: Specific topic – Splicing and splicing regulation b. Days 3: Specific topic – Regulation of protein translation c. Days 4-5: Specific topic - Epigenetic regulation of gene expression 1st Week (6-10 October) Monday 6
LC and FE will dissect topic 1 (transcriptional regulation of gene expression) with moderate detail. LC will provide a global perspective on how the modular functioning of regulatory elements and the cellular “transcription factor environment” govern cell type specific transcriptional programs. FE will lecture on how specific protein-protein and DNA-protein interactions govern the assembly of the transcription machinery onto regulatory elements to drive gene-specific transcriptional activation/repression. He will also highlight (with low detail) the power of physical techniques to dissect key molecular interactions occurring at the transcription unit. By the end of the first day students shall understand how highly specific molecular interactions govern the activity of specific sets of genes yet allowing flexibility and adaptation to intra- and extra-cellular cues. Tuesday 7
MGC and LR will dissect the mechanisms of splicing (MGC) and RNA quality control (LR). MGC will also introduce the usefulness of broad-scale approaches to our current understanding of coordination of gene expression at the post-transcriptional stage. Students shall understand how these two major post-transcriptional mechanisms – splicing and RNA quality control - coordinate to tailor the potential diversity of the human genome in order to ensure proper cellular/organism function. Also, how deregulation of these phenomena may lead to disease of blood (LR) and muscle (MGC) cells.
CMF will highlight the impact of controlling protein production in the secretory pathway, protein conformation and modification, and protein targeting to specific destinations along the secretory pathway, highlighting the different levels of the cellular mechanisms of quality control, to achieve a key goal of gene expression: "the right amount of the right protein at the right time in the right place". The human genetic disease cystic fibrosis will be used as a model to illustrate these processes. CA will focus on the pervading role of microRNAs in gene expression from gene transcription to protein translation. This will provide an important paradigm of how specific genes may influence the activity of other genes at multiple steps of their expression. Also, the relevance of bioinformatics and broad-scale analysis to disclosing real and predicted functions of microRNAs will be stressed. Thursday 9
IP will lecture on how coordinated regulation of gene expression at different steps (transcription, RNA and protein stability) generates molecular oscillatory mechanisms – “molecular clocks” – to govern key events during embryogenesis. Friday 10
LS will provide an overview of how genes influence other genes (gene networking) to set-up a transcriptional program in the context of embryonic development. LS will also tell of the power of large-scale approaches to unravel novel networking partners. JLA will deliver a seminar of broad, general interest entitled “Science and technology: means or ends”. 17:00 Beer hour
JT will lecture on the targeting of the splicing reaction in the context of the HIV infection. More specifically, how targeting the splicing of key HIV genes may be achieved with major effects in the production of HIV particles but little effect on the splicing of endogenous genes. Students shall understand how smart drug design and testing may foster the development of drugs that display differential targeting of gene expression (host vs pathogen). Tuesday 14
MC will lecture on the relevance of epigenetic effects in gene expression with a focus on how epigenetic factors acting during development affect fetal programming of adult disease and the metabolic syndrome (obesity, diabetes). MJS will deliver a seminar entitled “Transthyretin deposition in an animal model of familial amyloidotic polyneuropathy". The usefulness of animal models of human pathologies will be highlighted. All day: Preparation of student´s presentations for next Wednesday (15th); the tutors for the Gene Expression module shall be available.
AK will lecture on the connections between trombophilia and 3´mRNA processing efficiency. He will also address how the careful molecular analyses of specific types of trombophilia in children helped to unravel novel important aspects of the 3´mRNA processing mechanism. MA will explain how smart design of therapeutic vectors is planned to achieve insertion site independent, tissue type-specific expression of therapeutic genes. Students shall understand how the basic knowledge regarding regulatory sequence elements and tissue specificity of transcription factors, as well as regulation of chromatin structure, is to be applied to this specific aim. Thursday 16 All day: Preparation and presentation of papers selected by the students. Friday 17
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