Digital Public Defence: Gaia Calamera
Master Gaia Calamera at Institute of Clinical Medicine will be defending the thesis “Molecular and functional compartmentation of cGMP in the heart.” for the degree of PhD (Philosophiae Doctor).
Foto: Øystein Horgmo, UiO
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Click here to participate in the public defence
Download Zoom here
Digital Trial Lecture – time and place
See Digital Trial Lecture.
- First opponent: Professor Jin Zhang, University of California San Diego, US
- Second opponent: Associate Professor Konstantinos Lefkimmiatis, University of Pavia, Italy
- Third member and chair of the evaluation committee: Professor Hesso Farhan, University of Oslo
Chair of the Defence
Professor Henrik Huitfeldt, Faculty of Medicine, University of Oslo
Associate Professor Kjetil Wessel Andressen, Faculty of Medicine, University of Oslo
Cyclic GMP (cGMP) is a second messenger that, amongst others, regulate cardiac and vascular functions. Therapies that increase cGMP has shown several beneficial effects in the cardiovascular system. However, the mechanisms behind some of these effects in the heart are not fully understood.
In the heart, cGMP is synthesized by either NO-dependent activation of soluble GC (sGC) or natriuretic peptide-dependent activation of transmembrane-spanning GCs. Of these, GC-A is activated by atrial and brain natriuretic peptides (ANP and BNP), whereas GC-B is activated by C-type natriuretic peptide (CNP). To maintain homeostasis, increased levels of cGMP is degraded by different phosphodiesterases (PDEs).
The aim of the thesis was to investigate subcellular cGMP signalling in cardiomyocytes by measuring cGMP in real-time inside cells using various FRET-based biosensors. Moreover, we wanted to unravel the signalling pathways involved in heart relaxation and apoptosis of cardiomyocytes.
Applying targeted FRET biosensors in adult cardiomyocytes we show that GC-B, stimulated by CNP, increases cGMP around the sarcoplasmatic reticulum and the contractile compartment, reducing myocardial contractility (negative inotropic response) and accelerating myocardial relaxation (lusitropic response). Moreover, the specific PDEs that regulated these cGMP pools in adult cardiomyocytes were PDE2 and PDE3.
Furthermore, using mitochondrial targeted FRET biosensors, we show that stimulation of both GC-A and GC-B increase cGMP around the outer mitochondrial membrane, and this protects cardiomyocytes from apoptosis through modulating the mitochondrial function.
Considering that few FRET biosensor are currently available for cGMP, we also decided to develop novel FRET biosensors with high affinity for cGMP, and show their applicability in several cell types.
Overall, FRET biosensors are important tools to reveal organization of intracellular signalling pathways and to help understand how local cGMP pools are organised in specific cell locations and how these mediate functional responses.
Contact the research support staff.
Published Sep. 28, 2020 7:58 AM
- Last modified Oct. 9, 2020 9:51 AM