PAS mutation: roles in the local and global protein conformation - PHGY 396 Undergraduate Research Project Application Form

Supervisor's Name: Gergely Lukacs

Supervisor's Email: gergely.lukacs [at] mcgill.ca

Supervisor's Phone: (514) 398-5582

Supervisor's Website: https://mcgill.ca/physiology/directory/core-faculty/gergely-lukacs

Supervisor's department: Physiology

Course number: PHGY 396 (Physiology)

Term: Fall 2015-2016

Project start date: Friday, September 4, 2015

Project end date: Monday, December 7, 2015

Project title: PAS mutation: roles in the local and global protein conformation

Project description (50-100 words suggested): The human ether-a-go-go (hERG) gene encodes the pore-forming alpha subunit of a voltage-gated potassium channel expressed in the heart and in nervous tissue. Loss of function mutations usually result in protein misfolding and defects in trafficking, being the underlying cause of long QT syndrome type 2. These channels are tetrameric with each subunit containing a N-terminal PAS domain and a C-terminal CNBD domain contributing to channel assembly and regulation. The structural mechanism by which mutations upon these cytosolic domains affect local and global protein conformation remains unknown. The student will engineer a set of affinity-tagged wild-type and mutant PAS domain constructs. The domains will be purified from E. coli and characterized by using differential scanning fluorometry and hydrogen-deuterium exchange-mass spectrometry to explore their global and local conformational dynamics.

Prerequisite: 1 term completed at McGill + CGPA of 3.0 or higher; or permission of instructor.

Grading scheme (The final report must be worth at least 50% of final grade): Final report: 50%; Laboratory performance: 50%.

Project status: This project is taken. The professor has no more '396' projects this term.

Ethics, safety, and training: Supervisors are responsible for the ethics and safety compliance of undergraduate students. This project involves: Biohazardous substances; Handling chemicals.