SRP Diabetes Postdoc Fellowships - Project 3

Project title: Illuminating mechanisms linked to muscle dysfunction in peripheral artery disease.
Principal Investigator: Johanna Lanner
Department of Physiology and Pharmacology

Johanna Lanner

Lecturer senior
Molecular muscle physiology and pathophysiology
C3 Department of Physiology and Pharmacology

Research Project

Illuminating mechanisms linked to muscle dysfunction in peripheral artery disease.

Comorbidities of type II diabetes (T2D) are major health concerns worldwide, including peripheral artery disease (PAD). PAD lowers blood flow to the lower limb, causing muscle ischemia and dysfunction and reduced exercise tolerance. Functionality of limb skeletal muscle is a key component for determining morbidity and mortality risk in patients with PAD. Interventions that improve distal arterial pressures (ie. bypass surgery) generally fail to normalize the structural and functional abnormalities of muscles, which point towards pathophysiological mechanisms inside the skeletal myofibers that reduce overall muscle function. Despite serious muscle abnormalities, the field is lacking molecular understanding of PAD-induced muscle dysfunction. Here we aim to use a translational approach involving PAD patients and mouse models and state-of-the-art methods going from functional analyses to single cell profiling to illuminate molecular mechanisms underlying PAD-induced muscle pathophysiology. In the project, human skeletal muscle biopsies, as well as muscle from preclinical model, will undergo multiple assessments e.g., global transcriptomic analyses and single-cell profiling, histopathological analysis (electron microscopy, immunofluorescence), mitochondrial respiration, and contractility (force) measurements. Muscle cultures, isolated muscle fibers and in vivo models will be used for gain- or loss-of-function experiments to assess selected molecular candidates from the transcriptional analyses.  The expected outcome of this curiosity-driven project is detailed molecular understanding of intramuscular signaling and contractile function, which will yield substantial novel insights into PAD muscle pathology and identify targets for future therapeutic development.

Project description

Read the complete project description.

How to apply

Link to job posting at VARBI application portal.

The closing date for applications has been brought forward to midnight CEST on Sunday 15th May, 2022.