A Research-Inspired Biochemistry Laboratory

We have developed two “research-inspired” biochemistry lab modules, a total of sixteen laboratory sessions and six accompanying lectures, which now constitute the MIT undergraduate biochemistry laboratory sequence. The modules enable students to investigate a current and exciting research topic, drug resistance of the kinase Bcr-Abl in chronic myelogenous leukemia, while giving them experience in standard biochemistry techniques. Moving away from the organization of a typical lab course comprised of unrelated laboratory exercises, we strove to infuse this course with the excitement of true research by having the students execute a research plan from start to finish. The laboratory involves expression of the Abl kinase domain in E. coli, site directed mutagenesis to make an Abl mutant of the students’ choice from over thirty possible point mutations implicated in drug resistance, use of a spectrophotometric-coupled activity assay to probe for Abl-mediated phosphorylation, screening of the cancer drugs Gleevec and Dasatinib against wild-type and mutant forms of Abl, and analysis of published crystal structures to deduce the modes of kinase inhibition and drug resistance. The course provides students a hands-on understanding of the impact of chemistry on human health and illuminates the need for improved cancer therapies and the potential that they could be the next generation of investigators. The lab sessions incorporate frequent, discreet success points over the course of the semester and are therefore amenable to breaking upinto smaller modules for use by other schools with different time constraints. The lab has already been modified for use in a variety of other biochemistry programs across the country.

Following implementation of the laboratory modules in the Spring semesters of 2008 and 2009, students reported significant gains in all biochemistry skills tested in a learning gains assessment, with a self reported proficiency increase (on a 7-point Likert scale) from 3.0 prior to the course to 5.3 following the course, averaged over all skills. Students also responded with extremely high ratings of agreement with the following statements on the 2009 survey: “As a result [of this lab] I have a better understanding of how chemistry research can have a direct impact of human health and medicine” (6.2/7) and “I found that learning biochemistry techniques in the context of an overarching research project made learning more interesting” (6.0/7).

Publications and Online Resources

Taylor, EV, Fortune JA, Drennan, CL (2010) A Research-Inspired Laboratory Sequence Investigating Acquired Drug Resistance. Biochemistry and Molecular Biology Education, 38(4), 247-252.

(Note: This publication provides an overview, student data, student and instructor manuals, and supply/equipment lists for the expression and purification of the H396P Abl mutant, kinase assays with cancer drugs, and structure viewing. The mutagenesis will be published separately. This publication was designed for clarity and ease of use for other educators, so it more user-friendly than the OCW site below, which is a snapshot of the course in 2009 and is based on the MIT lab schedule. The OCW website, however, is the best place to go for the accompanying lecture notes and slides.)

MIT OpenCourseWare website of MIT course 5.36 in the Spring of 2009:

This website gives access to all of the lab and lecture-related materials for MIT course 5.36, a research-inspired biochemistry laboratory sequence at MIT. Web resources include detailed student and instructor laboratory manuals (organized for use as a comprehensive course or as selected sessions), equipment lists, and lecture slides and notes for accompanying background and technique lectures.