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RESEARCH LITERATURE IN MOLECULAR AND CELL BIOLOGY MCB 3841W Section 002 Fall 2010 Mary K. Bruno, Ph.D. Office: BPB 304 (Biology-Physics Building) Phone: 486-0360 E-mail: [email protected] Office hours: By appointment Lecture: MWF 9:00-9:50 AM TLS 263 TEXT: Readings for the course will include papers from the primary literature posted as PDF files on HuskyCT. Living Downstream, 2nd edition (written by Sandra Steingraber, Da Capo Press [Perseus Books Group], ISBN 978-0-30681869-1) Writing Papers in the Biological Sciences—Fourth Edition (Victoria E. McMillan Bedford/St. Martin’s Publishers, ISBN-13: 978-0-312-44083-1) PRIMARY COURSE OBJECTIVE: “Learning to write in a discipline means learning to think, argue, research and communicate with the community of scholars in a given field.” (excerpted from The Writing Center FAQ) ADDITIONAL COURSE OBJECTIVES: • To examine in detail current hypotheses addressing cell transformation and mechanisms of tumor development. To acquire an appreciation for the intricacy and balance that governs all of life’s processes. • To critically evaluate environmental factors as they impact on cancer risk. • To develop skill in analyzing and presenting research literature. • To foster good communication skills. All disciplines need excellent communicators. Scientists not only need to communicate the complexities of their field to fellow colleagues, but also to non-scientists, such as policy makers in government, industry, or in the biomedical field, to patients. MCB 3841W Fall 2010 1 ASSIGNMENTS: A minimum of 15 revised and edited pages of writing is a standard requirement for W courses. For MCB 3841W-002, this will consist of: • ONE 3-page paper in the style of a scientific commentary or editorial • ONE 5-page mini-review paper on a selective aspect of cancer biology (see list of topics) • ONE 5-page analysis of either environmental or epigenetic factors on cancer development • ONE 3-page essay based on Living Downstream • Two consecutive rounds of revisions for the writing assignment listed above Format: • • • • The type of paper (commentary, review, essay) must be indicated on the first page before the title The assignments should use a 10-12 point font and the text should be double spaced with 1 inch side and top/bottom margins Number pages. Header: Include your Name, Date that the paper is submitted followed by “Draft”, “Revision 1”, or “Final Version”. Other considerations: • As students in MCB, you are encouraged to read the primary scientific literature. It takes practice to become proficient or comfortable. Review articles have been provided to get you started. Bring questions to class if you are having difficulty with the reading. • Avoid the use of web sites in your citation list. Not all of them are reliable and you would be basing your paper on filtered, pre-digested information. (see URL info below to get started) • Do not rely heavily on one source for the basis of your paper. This introduces bias. Learn to understand arguments. Experimental data from different laboratories do not always agree. • Use the most current references (2008-2010) then work backwards if needed. This field moves at a very rapid pace. Older papers may give a perspective on the problem, but the conclusions or interpretations may have advanced considerably since that time—or may no longer be valid in the context of recent findings. Useful sites: • • • • **** http://www.ncbi.nlm.nih.gov/ http://www.plos.org http://www.cancer.gov/ http://www.cancer.org/ PubMed Public Library of Science National Cancer Institute American Cancer Society EVALUATION: • Your grade in the course will be composed of several components with the writing assignments comprising 70% of your grade. Class participation (see below) and the Final exam each will each represent 15% of your grade. • MCB 3841W Specific criteria will be provided with the assignment, however, general criteria for the evaluation of your assignments include: o Concise, focused thesis statement o Clarity, organized development of ideas or arguments o Transitions o Concise summary/conclusion—the bottom-line. o Grammatical errors, proofreading, incorporation of comments made on your drafts o Use of resources and appropriate documentation. Fall 2010 2 NOTE: A final submission for each assignment that contains multiple errors will not receive a passing grade. Statement from the Writing Center follows: According to university-wide policies for W courses, you cannot pass this course unless you receive a passing grade for its writing components. • Individual conferences may be scheduled outside of class time to further review and elaborate on improvement in writing practices. The conferences may be instructor or student-initiated. • Preparation and class participation are important components of the course; 15% of your grade will be based on this component. o o Readings for each topic should be done in advance to allow for class discussion. Each person will have an opportunity to present a segment of a published research paper for a journal club format discussion. Final exam: Rescheduling of the final exam requires the approval of the Office of Student Services and Advocacy. Statement from Office of Student Services and Advocacy follows: Final exam week for Fall 2010 takes place from Monday, December 13th through Saturday, December 18th. Students are required to be available for their exam during the stated time. If you have a conflict with this time you must visit the Office of Student Services and Advocacy to discuss the possibility of rescheduling this exam. Please note that vacations, previously purchased tickets or reservations, graduations, social events, misreading the exam schedule and over-sleeping are not viable excuses for missing a final exam. If you think that your situation warrants permission to reschedule, please contact the Office of Student Services and Advocacy with any questions. Thank you in advance for your cooperation. Colleges Against Cancer (CAC) For those of you with an interest in volunteering and writing reflectively about your experience, participation in UConn’s Chapter of Colleges Against Cancer may be an opportunity for you. More information can be found at the American Cancer Society’s web site as well as the Student Activities Involvement Office. DISABILITIES: Any student with disabilities that he/she would like the faculty to be aware of should communicate that information in confidence to the faculty and any issues arising will be addressed in accordance with the policy of the University. For more information, please go to http://www.csd.uconn.edu/ MCB 3841W Fall 2010 3 ACADEMIC MISCONDUCT STATEMENT: “Academic misconduct in any form is in violation of the University of Connecticut Student Conduct Code and will not be tolerated. This includes, but is not limited to: copying or sharing answers on tests or assignments, plagiarism, and having someone else do your academic work. Depending on the act, a student could receive an F grade on the test/assignment, F grade for the course, or could be suspended or expelled.” Policy On Plagiarism Plagiarizing is defined as “To steal and pass off (the ideas or words of another) as one's own : use (another's production) without crediting the source”(www.Merrian-Webster.com, 2005) Plagiarism violates the Academic Misconduct section of “The Student Code” of the University of Connecticut (http://web.uconn.edu/mcb201/misconduct.html) and will not be tolerated in MCB courses. The instructors of MCB 241W will adhere to the guidelines laid out in “The Student Code”; therefore, students should read and understand these policies and the consequence of violations. The definition of plagiarism extends to all aspects of evaluated work in this course. Copying another student's work is plagiarism. Failure to give full and proper citation to other people's work is plagiarism. Full and proper citation includes putting quotation marks around any quoted passage, including a correct citation to the publication from where the ideas originated and a complete reference to that publication in the "literature cited" section. This applies to all forms of communication including websites or personal communication from someone, such as would occur in verbal discussions of scientific data. Direct quotations are appropriate when the original statements would lose clarity or intent. However, your assignment should not include multiple direct quotations. Paraphrasing of other authors' work is acceptable given that the ideas contained in the paraphrased passage are properly attributed to the author and the ideas are reworded into the student's own original language. There are many resources available to students: PLEASE COMPLETE THE PLAGIARISM MODULE IN HUSKYCT. Should you need additional information the following web sites may be of help: http://www.lib.uconn.edu/using/tutorials/LILT/plagiarism.htm http://owl.english.purdue.edu/handouts/print/research/r_plagiar.html See also pp 29-30 and 124-126 in Victoria McMillan’s book The penalties for copying another students work are: 1. The first violation will result in a "0" for the entire assignment. 2. The second violation may result in an ‘F’ for the course. The penalties for failure to cite properly are: 1. The first violation will result in a written warning. 2. The second violation will result in a "0" for that assignment. 3. The third violation will result in a "0" for the assignment and failure in the course. MCB 3841W Fall 2010 4 Part 1: Why, when, how??? Development of cancer: old vs. current hypotheses “The chaos of cancer is not a modern affliction but a risk run by all multicellular organisms from ancient to modern.” Robert A. Weinberg, One Renegade Cell: How Cancer Begins DATE LECTURE TOPIC READING ASSIGNMENT # Numbers refer to reference list Aug 30 Sept 1 Sept 3 Sept 6 Sept 8 Sept 10 Sept 13 Sept 15 Sept 17 Sept 20 Sept 22 Sept 24 Sept 27 Sept 29 Oct 1 Oct 4 Oct 6 Oct 8 Oct 11 Oct 13 Oct 15 Oct 18 Oct 20 Oct 23 Oct 25 Oct 27 Oct 29 MCB 3841W Introduction / Historical Overview Free write / Discussion Properties of cancer cells / Hallmarks of Cancer LABOR DAY Controversies in cancer research Writing Workshop Examples of scientific writing Characteristics of scientific writing Review of grading rubric Hypotheses for cancer development Cancer stem cell hypothesis Cell signaling & the tumor microenvironment The tumor microenvironment Role of the EMT (epithelial-mesenchymal transition) The cell cycle and its regulation Oncogenes and tumor suppressor genes p53 and multi-tasking Journal club discussion Epigenetic mechanisms Milestones 1,2,4 #1 Milestones 9-12,14,17 #2-8 Review / skim Chapts 1,6, 7 in McMillan #9 #10.11 #12 Draft of Commentary Due Draft returned Chapt 7 in McMillan #13 Revision 1 Due #14 Revision returned #15 Chapt 5 in McMillan Commentary Final Version Due; Select topic for minireview & begin research Telomeres DNA damage: Apoptosis vs. Senescence? Angiogenesis and hypoxia Hypoxia and bioenergetics Metabolic requirements of cancer cells Metabolic requirements of cancer cells Journal club discussion Cancer and Inflammation MicroRNAs #16 #17 Chapts 6 & 7 in McMillan #18, 19 #20 #21-23 #24 Metastasis & the role of chemokines Writing workshop / Peer Review of Minireview Revision 1 #27, 28 Begin Living Downstream Forward & Chapts 1-4 (pp. 1-87) for Discussion on 11/10 Mini-review Draft Due Draft returned #25 #26 Mini-review Revision 1 Due Fall 2010 5 Part 2: Cancer—a preventable disease? Genetic, Environmental and Nutritional Factors “From the right to know and the duty to inquire flows the obligation to act.” Sandra Steingraber DATE LECTURE TOPIC READING ASSIGNMENT Nov 1 The cytochrome P450 system and genetic polymorphisms The cytochrome P450 system and genetic polymorphisms TBA Mini-review Revision 1 returned Mini-review Final Version Due Select Topic for Paper 3 & begin research Nov 3 Nov 5 Nov 8 Nov 10 Nov 12 Nov 15 Nov 17 Chemical carcinogenesis / Cancer clusters Environmental causes of cancer controversy Long Island Breast Cancer Study Discussion—Living Downstream (LD) Part 1 Epigenetics revisited Nutritional factors Discussion—Living Downstream Part 2 Nov 19 Writing Workshop / Peer Review of Paper 3 Draft Nov 2226 Nov 29 THANKSGIVING BREAK Living Downstream Chapts 5-6 (pp.89-141) for Discussion on 11/17 Paper 3 Draft Due Essay Questions for LD Paper 3 Draft returned Living Downstream Chapts 7-12, Afterword (pp.143-290) For Discussion on 11/29 Discussion—Living Downstream Parts 3 & 4 Paper 3 Revision 1 Due Part 3: Challenges of Therapeutic Measures “We propose that without a truly robust mechanism for selecting the right treatment for the right patient at the right time---the central concepts of personalized medicine---we will continue to see only incremental improvements and have little hope for substantial survival gains.” A.Potti, R.L.Schilsky, and J.R.Nevins (Science Translational Medicine, 2 (28), 1-3, 2010) DATE LECTURE TOPIC READING Dec 1 Dec 3 Overview of therapeutic approaches Multi-drug resistance TBA Dec 6 Dec 8 Dec 10 Dec 15 tentative Immunotherapies Personalized tumor biomarkers Course summary FINAL EXAM 8:00-10:00 AM MCB 3841W ASSIGNMENT Essay for LD due Paper 3 Revision 1 returned Essay for LD returned Paper 3 Final Version Due Revision of Essay Due Fall 2010 6 Reading List Part 1 1. Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell 100, 57-70. 2. Matloff, E.T. and Brierly, K.L. (2010) The double helix derailed: the story of the BRCA patent. Lancet 376, 314-315. 3. Kesselheim, A.S. and Mello, M. (2010) Gene Patenting—Is the pendulum swinging back? New England Journal of Medicine 362, 1855-1858. 4. Watson, J.D. NY Times Op-Ed: http://www.nytimes.com/2009/08/06/opinion/06watson.html?_r=1&sq=Cancer&st=cse&scp=6&pagewanted=print 5. Potti, A., Schilsky, R.L., and Nevins, J.R. (2010) Refocusing the War on Cancer: The critical role of personalized treatment. Science Translational Medicine 2 (28), 1-3. 6. Ledford, H. (2010) The cancer genome challenge. Nature 464, 972-974. 7. Weinberg, R.A. (2010) Point: Hypotheses first. Nature 464, 678. 8. Golub, T.R. (2010) Counterpoint: Data first. Nature 464, 679. 9. Negrini, S., Gorgoulis, V.G., and Halazonetis, T.D. (2010) Genomic instability—an evolving hallmark of cancer. Nature 11, 220-228. 10. O’Brien, C.A., Kreso, A., and Jamieson, C.H.M. (2010) Cancer stem cells and self-renewal. Clinical Cancer Research 16 (12), 3223-3120. 11. Korkaya, H. and Wicha, M.S. (2010) Cancer stem cells: nature versus nurture. Nature Cell Biology 12 (5), 419-421. 12. Li, L. and Neaves, W.B. (2006) Normal stem cells and cancer stem cells: The niche matters. Cancer Research 66 (9), 4553-4556. 13. Kalluri, R. and Weinberg, R.A. (2009) The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation 119 (6) 1420-1428. 14. Vousden, K.H. and Prives, C. (2009) Blinded by the Light: The growing complexity of p53. Cell 137, 413-431. 15. Esteller, M. (2008) Epigentics in cancer. N. Engl. J. Med. Vol. 358, 1148-1159. 16. Artandi, S.E. and DePinho, R.A. (2010) Telomeres and telomerase in cancer. Carcinogenesis 31 (1), 9-18. 17. Cotter, T.G. (2009) Apoptosis and cancer: the genesis of a research field. Nature Reviews Cancer 9, 501-507. 18. Zetter, B.R. (2008) The scientific contributions of M. Judah Folkman to cancer research. Nature Reviews Cancer 8, 647-654. 19. Jain, R.K. (2005) Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science Vol 307, 58-62. MCB 3841W Fall 2010 7 20. Denko, N.C. (2008) Hypoxia, HIF-1 and glucose metabolism in the solid tumor. Nature Reviews Cancer 8, 705-713. 21. Vander Heiden, M.G., Cantley, L.C. and Thompson, C.B. (2009) Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science Vol 324, 1029-1033. 22. Pollard, P.J. and Ratcliffe, P.J. (2009) Puzzling patterns of predisposition. Science 324, 192-194. 23. Thompson, C.B. (2009) Metabolic enzymes as oncogenes or tumor suppressors. New England Journal of Medicine 360, 813-815. 24. Olovnikov, I.A., Kravchenko, J.E. and Chumakov, P.M. (2009) Homeostatic functions of p53 tumor suppressor: Regulation of energy metabolism, and antioxidant defense. Seminars in Cancer Biology 19, 32-41 25. Grivennikov, S.I., Greten, F.R., and Karin, M. (2010) Immunity, inflammation, and cancer. Cell 140, 883-899. 26. Koturbash, I. et al. (2010) Small molecules with big effects: The role of the microRNAome in cancer and carcinogenesis. Mutation Research doi:10.1016/j.mrgentox.2010.05.006 27. Weinberg, R.A. (2008) Mechanisms of malignant progression. Carcinogenesis 29 (6), 1092-1095. 28. Teicher, B.A. and Fricker, S.P. (2010) CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clinical Cancer Research, 16 (11), 2927-2931. MCB 3841W Fall 2010 8