PhD project - Exploring the role of cullin-3 for muscle and motor neuron development as well as the etiology of neuromuscular myopathies , Aarhus university, Denmark, 2022

PhD position is available in Exploring the role of cullin-3 for muscle and motor neuron development as well as the etiology of neuromuscular myopathies at Graduate School of Health, Aarhus University, Denmark, 2022

Qualification Details

The applicant should have prior knowledge and experience in basic methods for molecular biology, biochemistry and cell biology. Prior knowledge and experience in muscle cell differentiation, isolation of primary cells, animal work (mouse) and muscle physiology are highly desirable. Knowledge in next generation sequencing, proteomics and/or metabolomics is advantageous. The applicant should possess a Masters Degree (or comparable). The applicant should be fluent in spoken and written English. Knowledge of Danish or another Nordic language is advantageous. In the assessment of prospective candidates, applicants will be shortlisted.

Responsibilities/Job Description

Motor neurons in the brain and spinal cord connect to muscles tissues in the body. This allows for muscle contraction and growth, resulting in body movement or breathing. The interface between motor neurons and muscle cells is called neuromuscular junction (NMJ). Impairment of motor neurons or skeletal muscles results in neuromuscular disorders. Treatment options are limited, and these disorders impose a major burden on the individual and society. Many neuromuscular disorders are caused by faulty protein degradation: either prematurely degrading proteins, or failing to degrade old or faulty proteins. The main degradation machinery for proteins is the ubiquitin-proteasome system. It involves enzymes, such as E3-ligases that control which substrates are marked for degradation. Ours and published data show that cullin-3, one of these E3-ligases, and its associated proteins are essential for NMJ formation and muscle function. Loss of cullin-3 or mutations in its associated proteins and substrates results in several neuromuscular disorders. There are compelling similarities between clinical features of patients suffering from neuromuscular disorders and the phenotypes of muscle specific cullin-3 knockout (KO) mice, KO mice for cullin-3 adaptor proteins and mutant proteins in motor neurons whose degradation is dependent on cullin.These data are in strong support of our hypothesis, that cullin-3 mediated protein degradation plays crucial roles for motor neuron function, proper formation of neuromuscular junctions and functioning muscles. The overall goal of this three year PhD project is to uncover the molecular roles that cullin-3, its adaptors and substrates play in the formation and function of motor neurons, muscles and in the etiology of neuromuscular disorders, by pursuing the following objectives: 1) Study physiological and phenotypical effects of cullin-3 loss in motor neurons 2) Determine molecular roles of cullin-3 and its adaptors 3) Study cullin-3 linked pathomechanisms for myopathy development

How to Apply?

Application Method: online_applicationRef. No. -

Application Procedure

For information about application requirements and mandatory attachments, please see our application guide

Note or Other details

For information about application requirements and mandatory attachments, please see our application guide

Contact Details

Please contact Associate Professor Stephan Lange, stephan.lange@biomed.au.dk, for further information.