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PhD Defense by Christian Holt

Christian Holt, Department of Chemistry and Bioscience will defend his thesis on: "Calmodulin Mutations Alter the Structure and Interaction with Cardiac Calcium Channels"

Time

13.12.2018 kl. 09.00 - 12.00

Description

TITLE:

"Calmodulin Mutations Alter the Structure and Interaction with Cardiac Calcium Channels"

ABSTRACT:

The human heartbeat is generated by the excitation and contraction of cardiomyocytes and is tightly regulated by intracellular Ca2+-signals. Even the smallest perturbations in any of the signals leading to the generation of a heartbeat, can lead to arrhythmias or even cardiac arrest.

Calmodulin (CaM) is a small intracellular Ca2+-binding protein which mediates Ca2+-signals to several hundred different targets including some of the cardiac ion channels participating in the generation of a heartbeat. CaM is one of the most conserved proteins being 100 % identical among all vertebrates. Recently identified mutations in one of the three genes encoding CaM were shown to lead to severe ventricular arrhythmias.

In this thesis some of the identified CaM mutants are investigated with high-resolution techniques to unravel the underlying mechanism causing the arrhythmia. Utilizing both X-ray crystallography and NMR, structures of the CaM mutants are elucidated along with the structures of CaM mutants in complex with the calmodulin binding domains from the cardiac voltage-gated Ca2+-channel, CaV1.2, and the cardiac ryanodine receptor, RyR2.

SUPERVISOR:

  • Professor MSO Reinhard Wimmer, AAU

ASSESSMENT COMMITTEE:

  • Associate Professor Peter Kristensen, Institut for Kemi og Biovidenskab, Aalborg Universitet, (Chairman)
  • Assoc. Prof. Klaus Zangger, Institute of Chemistry / Organic and Bioorganic Chemistry, Karl Franzens Universität
  • Lektor Frans Mulder, Department of Chemistry, Aarhus Universitet

AFTER THE DEFENSE A SMALL RECEPTION WILL BE HELD AT FREDRIK BAJERS VEJ 7H. 

Price

Free

Host

Department of Chemistry and Bioscience, AAU, Section of Biotechnology

Address

Fredrik Bajers Vej 7H, 9220 Aalborg Ø, room number: Auditorium