BIOS 743 Genomics, Proteomics and Bioinformatics Instructors: Professor Lance Liotta MD PhD (Room 323 Bull Run Hall) and Professor Emanuel Petricoin PhD (Room 324 Bull Run Hall) Thursdays 4:30-7:10 p.m. at the Prince William campus, Bull Run Hall Room 248 Office Hours: Thursdays 230-430 Room 323 and 324 Bull Run Hall and by appointment (contact Ms. Peggy Hackett, phackett@gmu.edu) Description of the course: The new era of personalized therapy and molecular medicine is a perfect example where the functional aspects of genomics, proteomics and bioinformatics comes to together at the bedside. This course will focus on the practical use of these three areas for the diagnosis, prevention and treatment of disease. Real world case studies will be used to illustrate and educate students, as well as touch on the downstream issues in regard to the regulation of such new platforms and assays. - Week 1 Jan 24 Instructor: Liotta Introduction to the course. Cancer Molecular Biology and introduction to cellular proteomics and genomics. Discussion of basic principles of molecular medicine, including the definition and the need for individualized diagnostics and therapeutics. Review of cancer medicine and the basics of cancer molecular biology. Functional principles of protein synthesis, protein folding, receptors, protein functions, and protein signal transduction. Review of the major advances in these fields which have relevance to molecular medicine of the future - Week 2 Jan 31 Instructor Petricoin Introduction to genetics and genomics. Sequencing the human genome, Cancer genomics, cancer transcriptomics. Review of the major advances in these fields which have relevance to molecular medicine of the future. Application of genetics and genomics to the prediction of disease. - Week 3 Feb 7 Instructor Luchini Nanotechnology Guest Professor: Alessandra Luchini Introduction to the definitions and principles of nanotechnology. Microfabrication nanomachines, nanofluidics, application of nanotechnology to personalized therapy and the future of molecular medicine. - Week 4 Feb 14 Instructor: Vaisman Introduction to Bioinformatics: Guest Professor: Iosif Vaisman Definition bioinformatics. Review of bioinformatics tools. Data categories and reliability of data. Sources of bias and variability. - Week 5 Feb 21: Instructor: Espina Clinical chemistry and clinical pathology: applications to proteomics, genomics and bioinformatics. Guest Professor: Virginia Espina Review of tissue and blood clinical chemistry principles. Specimen collection, fixation, histologic examination and scoring, sources of bias in clinical research trials, definition of sensitivity, Tissue microdissection, precision, and accuracy. - Week 6 Feb 28: Instructor: Russo Mass Spectrometry techniques applied to proteomic-based biomarker discovery. Guest Professor: Paul Russo Principles of mass spectrometry. Differences between MALDI and ES. Introduction to ETD. and MRM. Software and bioinformatics tools for scoring and identification of candidate protein sequences. Post translational modifications in proteins. Application of Mass Spectrometry to the discovery of biomarkers for human disease. Blood biomarkers. Bottom up versus Top down approach. Discovery versus validation. Correct design of a discovery and validation trial. Examples of recent findings related to cancer diagnosis. - Week 7 March 7: MIDTERM EXAM - Week 8 March 14: Spring Break No Class - Week 9 March 21: Liotta Next generation multiplex Assay Technology for Proteins. Immunoassay principles. Antibody validation, Protein arrays, Particle and bead assays, Biosensors, Plasmon Resonance, Flow Cytometry. Examples of applications to cancer diagnostics. - Week 10 March 28: Petricoin Next generation Multiplex Assay Technology for genomics. Hybridization principles. Array platforms, Transcript arrays, RNA versus DNA, DNA methylation, Examples of applications to cancer diagnostics. Regulatory considerations for high complexity testing and multi-analytes. - Week 11 April 4 Instructor: Sharrer Medical Ethics in the Era of Genomics and Proteomics: Guest Professor: Terry Sharrer Ethics of Clinical research trials and incorporation of Omic technologies into clinical trials. - Week 12 April 11 Instructor: Mueller Focused Proteomic Analysis: Kinases, Phosphatases, and Nitric Oxide: Role in health and disease. Basic enzymatic principles, role in cell biology and diseases, therapeutic strategies, and relevance to individualized therapy -Week 13 April 18 Project Class Presentations - Week 14 April 25 Project Class Presentations - Week 15 May 2 Project Class Presentations - Week 16 May 9 Final Exam Additional references and project topic ideas will be provided during the course discussions. Grades will be based on: Mid Term Exam: 33% Final Exam: 33% Project Presentation: 34% Fundamental questions of Molecular Diagnostics, Proteomics, Genomics and Bioinformatics that one should address during this course. 1. What is the current and future role of molecular diagnostics in medicine? 2. What is the definition of individualized therapy and what are the implications for medical care and the biotechnology community? 3. How is cancer diagnosed and treated today? How is this envisioned to change in the future? 4. How do nucleic acids and proteins differ in their functional role in disease pathogenesis? 5. What are the current tools for measuring nucleic acids and proteins? What are the challenges and limitations of conventional measurement technologies? 6. Explain the requirements for biomarker clinical validation. 7. What are some of the emerging technologies and bioinformatics tools to measure genetic and proteomic molecules in tissue and body fluids? 8. Provide real world case studies for the application of individualized therapy to human disease.