Identification of the Molecular Determinants Delineating Functional Behavior in COX-1 Versus COX-2

Crystal Structure of COX-2 bound with substrate.

Structure-Function studies on NSAID-targeting enzymes. 

Project is Not Currently Available

This project is not being offered for the current term. Please check back next semester for updates.

Project description

The cyclooxygenase enzymes (COX-1 and COX-2) catalyze the committed step in the biosynthesis of prostaglandins. COX-1 and COX-2 are the pharmacological targets of nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, while COX- 2 is selectively inhibited by Celebrex and Vioxx. The objective is to evaluate how sequence differences between COX-1 and COX-2 influences the differential regulation of COX catalysis and inhibition observed between isoforms. The student will utilize kinetic and biophysical characterizations of mutant forms of COX-1 and COX-2 to evaluate sequence differences in specific regions of each enzyme. 

Project outcome

The goal is to expose undergraduate students to biomedical research by providing them with hands-on experiences. A student will be extensively trained and specifically tasked with techniques involved generating mutant enzyme constructs, overproduction and isolation of mutant enzymes and subsequent functional characterization of the enzymes. Research results will be formally presented within the Departmental seminar series at the end of the project period. The expectation is for the student to present research findings in poster format at a research symposium held on campus or at a neighboring Institution. 

Project details

Timing, eligibility and other details
Length of commitment Longer than a semester; 6-9 months
Start time Spring (January/February 2025)
In-person, remote, or hybrid? In-Person Project (Can only function with in-person engagement)
Level of collaboration Individual Student Project
Benefits Stipend
Who is eligible Juniors & Seniors; background in introductory courses in chemistry and biochemistry is preferred

Project mentor

Michael Malkowski

Professor and Department Chair

Structural Biology

Phone: (716) 829-3698

Email: mgm22@buffalo.edu

Start the project

  1. Email the project mentor using the contact information above to express your interest and get approval to work on the project. (Here are helpful tips on how to contact a project mentor.)
  2. After you receive approval from the mentor to start this project, click the button to start the digital badge. (Learn more about ELN's digital badge options.) 

Preparation activities

Once you begin the digital badge series, you will have access to all the necessary activities and instructions. Your mentor has indicated they would like you to also complete the specific preparation activities below. Please reference this when you get to Step 2 of the Preparation Phase. 

  1. Read Malkowski 2017 Cyclooxygenase structure review
  2. Read Sedjiu 2020 COX-1 MD simulation paper 

Keywords

structural biology, biochemistry, Jacobs School of Medicine and Biomedical Sciences