Principals of Biomedical Research Guri Tzivion, PhD tzivion@windsor.edu PBMR 611: Winter 2016 Windsor University School of Medicine Journal Club Instructors Dr. Soumitra Chakravarty Biochemistry Group 1 Dr. Samuel Taiwo Pre Med Program Group 4 Dr. Vivek Joshi Biochemistry Group 2 Dr. Fatai Oluyadi Pathophysiology Group 5 Dr. Bikramajit Singh Saroya Pathophysiology Group 3 Dr. Kusai Salhanie Pathophysiology Group 6 Course Description The Journal Club aims to: • Train the students in critical reading of biomedical research papers • Provide a venue for discussing recent scientific advances in the biomedical research field • Improve the scientific communication skills of our students Journal Club Presentation format: • Introduction to the subject area: General review of the subject What was known before the authors started their work • The declared hypothesis and objectives of the study • Methodologies used in the study • Results: Present the actual results of the study Discuss each of the figures in detail Journal Club Presentation format: • Discuss the significance of the study and its contributions to advancing the subject area/field (as presented by the authors) • Your critical analysis of the study: Strengths and weaknesses If you were the reviewer of the paper, what would be your critique? Journal Club Other points to consider in preparing your presentation: • Have a simple title for each slide • Fonts should be large enough to be seen clearly from the back of the room • Figures: for multi-panel figures, enlarge and show each panel separately Journal Club Presentation skills: • Be familiar with the presentation content • Speak loudly and clear • Speak with excitement, don’t be monotone • Do not read the slides – use the text as reference • Face the audience, make eye contacts • Use body language (facial expression, gesture) • Do not abuse the pointer Student evaluations Block Exam 1: 25%. Will cover topics 1-2 and material from the journal club Block Exam 2: 25%. Will cover topics 3-4 and material from the journal club Journal Club Paper presentation: 35% 15%: instructor evaluation of student participation in journal club discussions Journal Club Presentation evaluation grid: • Familiarity with the subject (20%): • Presentation skills (20%): • Stimulation of group discussion (20%): • Preparedness (20): • Overall presentation quality (20): • Final evaluation: • Comments for the student: Journal Club 1st theme: longevity research and sirtuin activators 1. Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6. 2. Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. 3. Hubbard BP and Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014 Mar;35(3):14654. Journal Club 2nd theme: B-Raf mutations and their targeting in Melanoma 4. Davies H, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949-54. 5. Tsai J, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6. 6. Bollag G, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010 Sep 30;467(7315):596-9. 7. Sosman JA et al. Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib. N Engl J Med 2012; 366:707-714. Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa1112302 Journal Club 3rd theme: Diabetes and high cholesterol management 8. Knowler WC, et al. "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin". The New England Journal of Medicine. 2002. 346(6):393-403 Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa012512 9. Patel A, et al. "Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes". The New England Journal of Medicine. 2008. 358(24):25602572. Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa0802987 10. Kastelein JJ, et al. "Simvastatin with or without ezetimibe in familial hypercholesterolemia". The New England Journal of Medicine. 2008. 358(14):1431-1443. Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa0800742 Enzymatic activity of sirtuins Regulation of Sir2 during calorie restriction in yeast Resveratrol Bordone and Guarente Nat Rev Mol Cell Biol 200 Mammalian sirtuin isoforms Subcellular localization of Sirtuin isoforms De Oliveira et al, Frontiers in Pharmacology 2012 Sirt1 functions and regulation The diverse physiological roles of the sirtuins Finkel et al. Nature 460, 2009 Structure of sirtuin activators used in the study Effects of resveratrol and caloric restriction on yeast life span and its dependency on sir2 and pnc1