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the case of Gene Regulation in Cells Background Gene regulation is the process of turning genes on and off in the right cells, at the right times, and in the right amounts. When a gene is turned on, the protein that it encodes is produced by the cell via transcription and translation. Proteins are the molecular machines that carry out the functions that cells need to perform, so the exact mix of proteins in a cell determines its cell fate (what kind of cell it is, for example making a neuron different from a skin cell). Therefore, gene regulation links genotype (genetic information) and phenotype (observable characteristics). The proteins that control gene regulation are transcription factors. They bind to DNA sequences called enhancers. When bound together, an enhancer and transcription factors act as a genetic switch to turn a gene on or off. (See box, “Gene Switches in Action,” Carroll et al., 2008). Evolutionary changes to an enhancer will change the location, timing, or amount of gene expression without changing the function of the gene itself. This can lead to new combinations of proteins in cells, and therefore to new phenotypes for the animal. While many enhancers are conserved among closely related animals, examples of new, lost, or modified enhancers have been discovered. You will read about multiple such examples in Carroll et al., 2008. Eric Bertolino of the University of Chicago studies regulatory networks that dictate cell fate choices in the immune system. Rebecca Spokony, a postdoc at the University of Chicago, is developing resources to study transcription factors in Drosophila melanogaster. By attaching a green fluorescent protein tag to the transcription factors their location can be studied visually and their genome-wide DNA binding patterns can be studied biochemically. For more information, visit the following websites: igsb.org/people/rebecca-spokony, http://www.igsb.org/ labs/kevin-white/ and http://mgcb.uchicago.edu/phd_program/faculty/singh/index.html. Lesson Overview Systems biologists are interested in understanding how the presence and absence of different molecules affect protein synthesis. In this lesson, students will learn about gene regulation in cells and then apply this knowledge by identifying analogous parts and processes in a given model—a city, factory, ecosystem, or other system. At the end of the lesson, students should be able to articulate how their model is analogous to gene regulation in cells and its relationship to systems biology: understanding cells as a functioning system can help us understand how systems work in general (e.g. the functioning of a whole ecosystem). The Field Museum • Chicago Center for Systems Biology The Case of Gene Regulation in Cells • Page 1 Essential Questions • Why is gene regulation important in cells? • What would happen if there were not inducers or inhibitors in cells? • How is the functioning of gene regulation analogous to an every day example, situation, or place? Objectives Students will… • Describe the function of gene regulation, inducers, and inhibitors. •Develop a model and label the parts and processes analogous to gene regulation in cells. •Engage in scientific inquiry to strengthen skills of critical thinking, questioning, deductive reasoning, and the scientific process. •Relate this project to systems biology and understand the effect of gene regulation on living cells and the whole organism. Next Generation Science Standards HS-LS1-1. C onstruct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells. HS-LS1-2. Develop and use a model to illustrate the hierarchical organization of interacting systems that provide specific functions within multicellular organisms. Common Core State Standards CCSS.ELA-Literacy.SL.9-10.4 Present information, findings, and supporting evidence clearly, concisely, and logically such that listeners can follow the line of reasoning and the organization, development, substance, and style are appropriate to purpose, audience, and task. Prerequisite Knowledge • What is regulation and why it is important • Understand transcription and translation •Understand the role of inducers and inhibitors •Important terms: DNA, RNA, protein, transcription, translation, inducer, inhibitor, ribosome, protein synthesis, genotype, phenotype, analogy/analogous, gene experession, cell differentiation Materials • Large sheets of paper (1 per team) • Markers and colored pencils (1 set per team) •Carroll, S.B., Prud’homme, B., and Gompel, N. (2008). Regulating Evolution. Scientific American, May, 60-67. http://www.ibdml.univ-mrs.fr/equipes/BP_NG/publications-files/Carroll2008.pdf (1 per student) The Field Museum • Chicago Center for Systems Biology The Case of Gene Regulation in Cells • Page 2 Time Frame The time frame for this project is subjective. A total estimated time of 125–165 minutes is suggested. Teachers can lengthen or shorten the time spent on each part of the project. An approximate time frame for each part is provided within the procedure. Assessment • Informal assessment through discussions • Poster and final presentation • Lab journal or write up including questions answered during the project Procedure Part 1: Introduction (20-30 minutes) •Review gene regulation in cells by having the students’ jigsaw (Break the students into small groups and assign each member of a group a page or two of the article. After reading their assigned pages the students come back to their groups and give an overview of their pages.) of the journal article Regulation Evolution, Scientific American. Part 2: Designing Models (75-90 minutes) •Provide background information about models and analogies, what they are and why they are helpful in illustrating complex concepts. For example, the human skeleton is like the framework of a house. Both give structural support. The skeleton allows the human to stand upright and supports the body and its internal organs; the framework of a house allows the house to stand upright without falling over and supports the roof and all floors/levels inside of the house. •Organize students in small groups. Each group should create a poster or blueprint of a model (city, factory, ecosystem, or other system) analogous to the process of gene regulation. Posters should include a title and all relevant parts and processes labeled (what it is, an explanation of its function, and its analogous part or process/ function within gene regulation). Part 3: Presentation and Discussion (30-45 minutes) • Have teams present their models. •Conduct a summative discussion to connect the project with gene regulation in cells and how this relates to systems biology: understanding the functioning of cells (cells as a functioning system) can help us understand the workings of a system (e.g. the functioning of a whole ecosystem). Funding and support provided by NIH & CCSB. The project described was supported by award number P50GM081892 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences of the National Institutes of Health. The Field Museum • Chicago Center for Systems Biology The Case of Gene Regulation in Cells • Page 3