This course will provide students with an understanding of the scientific principles underlying the toxic actions of various substances that have a profound impact on human health. In addition, they will be provided with an in depth survey of advanced molecular laboratory techniques used to investigate these phenomena by a careful examination of the current literature. The chemical nature of toxic substances, their mode of action, and the impact that they have on gene regulation will be emphasized. Molecular biological techniques for interrogating genomes at the epigenetic level will be introduced. Finally, students will be introduced to the topics of pharmaco-/toxico- genetics and genomics and bioinformatics and quantitative approaches necessary to analyze these studies. This course is designed to prepare graduates who have an interest in medicine and human health services to pursue careers in these disciplines. In addition, this course will serve as one of the units in the training of the lab-based graduate students in the area of chronic disease and Environmental and Occupational Health in the Faculty of Health Sciences.

Course Outline:   

Week 1   Principles of Geno-phamacology/toxicology – Control of Gene Expression:  In this lecture students will be introduced to the core concepts of this course as they relate to the impact of environmental determinants of gene expression.  Topics will include a brief review of the molecular mechanisms of gene transcription, transcription factors (such as ligand-activated) receptors, and DNA/chromatin structure.  In addition, students will be provided with introductory literature and they will be assigned specific peer-reviewed publications for review and presentation.    

Week 2 (i) The control of eukaryotic gene transcription, and; (ii) Genes and the environment.   Papers on relevant topics will be assigned. 2.  Group presentation topics assigned. Discussions should include an overview of the topic with special regard to relevance to environmental health.  In addition, reviews should chart the “history” of the collective research from toxicity to molecular mechanism, and should include a brief outline of the experimental design/methods used.    

Week 3  Small molecule therapy and drug design.  Current methods in drug discovery will be presented including mono-clonal antibody therapy, peptide drug action and rational design of synthetic small molecules.   1. Critique Paper assigned – students will be assigned a specific paper and asked to critique it based additional information cleaned from online literature search tools.  Critiques should be 3-4 double-spaced pages.  They should highlight the key findings, discuss the validity of the findings and the rigor of the study with special detail to experimental design.  In addition, students should comment on the impact of the investigators findings for the field on environmental health.    

Week 4  (i) Toxico-genomics and;
(ii) Experimental Methods including next generation high-throughput sequencing techniques, CRISPR-Cas9 gene editing techniques, and mouse models will be presented.    

Week 5  Group Presentations and group discussion    

Week 6 (i) Group Presentations and group discussion;  

Week 7 (i) Critique Paper Due. Critiques should be 3-4 double-spaced pages.              
(ii) Endocrine disruption, cancer and solid tumour cell transformation  

Week 8  CRISPR-Cas9.  Current methods in genetic manipulation as pharmacological does and therapy.  

Week 9  Epigenetics:  DNA and chromatin modifications that affect gene expression and how these modifications are sensitive to environmental cues will be reviewed.  In addition, current methods and topical conceptual problems will be presented.  Papers on relevant topics will be assigned.  

Week 10  Paper presentations/Peer-reviewed draft proposal critique/evaluations:   

Week 11 (i) Guest Lecture:  Dr. Nadine Provencal – Molecular mechanisms of chromatin remodeling and cancer.  
(ii) Student paper presentations.  

Week 12  Undergraduate student presentations.  

Week 13  (i) Graduate student presentations (776 component) – Environment, disease and experimental therapeutics.              
(ii) course wrap-up.

The objectives of this course are to expose students to current molecular biological protocols, paradigms and stratagies that are commonly used in modern analytical and research lab settings. Students should be able to demonstrate knowledge of the principles of epigenetics and gene regulation as they relate to the physiology of drug and toxicant action in the body. In addition, students should be able to examine a peer-reviewed article and clearly articulate the hypothesis, the main finding(s) and critically evaluate the rigour and validity of the study. To support their critiques, students should be able to cite relevant findings in the literature. By the end of the course the students should be comfortable describing multiple approaches to molecular based methodologies for interrogation of the genome as it relates to human physiological adaptation to environmental stress and cues. In particular, students should be able to demonstrate firm understanding of toxico-genomics and the quantitative approaches used to interpret broad-based genomic studies regarding topical pharmaco-toxicological issues in human health.