Semester Schedule and Alignment with the 9 Essential Elements of Research
This CURE was designed for introductory chemistry students in a lab class of 18-20 students at three different institutions, University of San Diego, Southwest Community College and Gaston Community College. The CURE can be taught as either a full semester CURE (14 4 hour lab periods) or as a 6 week modular CURE (4 mornal lab periods) within a standard laboratory class. It is suitable for students in an introductory level chemistry class and requires no specialized knowledge. This CURE is readily adaptable to any disease or potential drug target
CURE Design
The research theme at the heart of this CURE is a perenial problem facing drug development- how can you achieve specificity for a pathogen target when host homologs exist. The CURE starts with discussions of the target enzyme, Malate Dehydrogenase and what it does in both pathogen and host and introduces some basic ideas of both orthosteric and allosteric drugs. Students then decide which approach they want to pursue, do background reading into Malaria start to pose questions of what they need to know or be able to do to uniquely targt the pathogen MDH. They start some bioinformatics and protein visualization approaches and develop ideas for compounds they would like to screen (including high throughput screening, screening extracts of natural products eg herbal extracts etc), making a hypothesis and developing their research proposal. They screen potential "drug-like" molecules based on known or potential orthosteric ligands using enzyme inhibition kinetics, and explore potential cryptic allosteric sites computationally all the time using pathogen target and human homologs. They explore Lipinsky rule of 5 properties both experimentally, determining logP, or structure-activity relationship properties computationally. As part of their experiments they learn and apply appropriate data analysis and display approaches, and accurate recording of experimental details and data archiving before selecting, based of their hypothesis and actual data they collected which experiments need repeating to validate their evidence based conclusion. In each stage the course uses peer review of presentations on critical elements of the research enterprise and student shave the chance to revise based on feedback prior to grading
Depending on the approach they chose to use there are a variety of potential stake holders, and students are encouraged to think about this aspect and communicate as appropriate their plans early in the course and research products at the end of the course, explaining why there is a continual need for new antimalarial drugs and what approach they have chosen to pursue.
Tasks that Align Student and Research Goals
Research Project Goals
Research Goal 1: To develop ideas for potential lead compounds that can distinguish between pathogen and host homologs of a potentail drug target
Research Goal 2: To initiate potential approaches for optimizing the potential of such lead compounds to increase their suitability as candidates for potential future drug design
Student Learning Goals
Student Goal 1: Students will appreciate what a good research project entails and will develop approaches to develop a novel hypothesis and present a proposal for their project
Student Goal 2: Students will learn how to design and execute experiments to test their hypothesis, will learn appropriate data analysis approaches and will appreciate the importance of accurate documentation of their work and reproducibility of their experiments.
Student Goal 3: To develop a description of their research project in written, poster or a slide presentation suitable for verbal presentation
USD: Week by Week Powerpoints, Class Room Activities and Templates
We start by exploring the nine essential components of research. Students learn to use molecular visualization, PyMol, MolView and POCASA to compare and contrast both target proteins (MDH from pathogenm asa well as human isoforms) and known ligands of MDH. Students are provided with templates for each aspect to guide their thinking and to record their observations. They produce a research proposal that is peer reviewed, revised and graded against a rubric they are given.
Students use computational docking of ligands to target to explore specificity and affinity for potential binding sites. Students are encouraged to use structure activity relationships to attempt to design new ligands and maximize specificity and affinity. They are provided with a template to recod their thinking and approach and results.
Student Goal 2: Students will learn how to design and execute experiments to test their hypothesis, will learn appropriate data analysis approaches and will appreciate the importance of accurate documentation of their work and reproducibility of their experiments.
Students design appropriate experiments, make up reagents, learn how to use appropriate equipment (balance, pH meter, spectrophotometer and pipettors) using a badging system of assessment of student abilities. Again they are provided templates for their experiments to record essential detail etc and to record primary data as well as how to appropriately analyze their data
Students determine LogP determinations using phase separation of specific compounds and use MolView to explore Lipinsky Rule of 5 properties of compounds
Powerpoints
Essential Elements Templates
Student Assessment Rubrics