Naturwissenschaftlicher Doktorand / PhD position (m/f/d)

Your tasks:

The AG Engel looks for a PhD candidate (65%, starting as soon as possible). The PhD position is integrated in the BMBF-funded consortium “Functional Autoantibodies targeting G-protein-coupled receptors (GPCR) in patients with ME/CFS (FAME)”. The person will mainly work with hiPSC-cardiomyocytes and M2 receptor agonists and positive chronotropic GPCRs antagonists. Goal is to test human sera for an effect on hiPSC cardiomyocytes. All our standard assays have to be utilized (e.g. contractility, calcium handling) and assays need to be established to visualize GPCR signaling (experience in cloning would be an advantage). Besides this specific project the PhD student should work on cardiac tissue engineering/biofabrication

Comments:

The project: Functional Autoantibodies targeting G-protein-coupled receptors (GPCR) in patients with ME/CFS
(FAME)
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a post-infectious complex systemic
disorder with post-exertional malaise (PEM) as the major symptom. Recent studies reported
on autoantibodies targeting G-protein-coupled receptors (GPCR-AAb) in patients with ME/CFS. The
available ELISA-based assays to detect the GPCR-AAb cannot discriminate between functionally
active and inactive GPCR-AAb and their clinical value has been disputed because of unspecific
reactions and high seropositivity even in healthy subjects. The lack of widely available robust bioassays
for the detection of functionally active GPCR-AAb (GPCR-fAAb) has made it difficult to elucidate
the role of GPCR-fAAb for the pathogenesis of ME/CFS. Our consortium observed GPCR-fAAb in a
subgroup of patients with Post-COVID, whose symptoms overlap with ME/CFS, and linked them to
an impaired retinal microcirculation. Therefore, the aim of this collaborative project is to delineate
the role of GPCR-fAAb in a cohort of patients with ME/CFS. For this purpose, bioassays will be
established for detection of GPCR-fAAb with focus on the muscarinergic receptor-fAAb. In addition
to our previously established rat cardiomyocyte assay, new assays will be developed based on human
inducible pluripotent stem cells (hiPSCs)-derived cardiomyocytes. This project will address the
following research questions:


I) What is the prevalence of GPCR-fAAb in adults and infants with ME/CFS?
II) Do GPCR-fAAb correlate to a clinical phenotype?
III) What are the infection-related triggers for the generation of GPCR-fAAb?
IV) What are the consequences of GPCR-fAAb binding to cellular target structures?


This research project will clarify the role of GPCR-fAAb in the pathogenesis of ME/CFS and provide
important data for a rational development of therapies for ME/CFS. In addition, the establishment of
new assays for the detection of GPCR-fAAb will provide new tools for the diagnosis and clinical care
of patients with ME/CFS.

Essential experience/qualifications:

• Diploma or Master's degree in Biology, Chemistry, Biochemistry, Molecular Medicine or equivalent
• English language skills
• As the fund starts in september we are looking for someone who can start as soon as possible, which means the person should be ideally already living in germany/europe
• highly motivated and reliable

Additionally beneficial are:

• hiPSC culture or cell culture in general
• hiPSC differentiation in cardiac muscle cells
• Tissue engineering/biofabrication
• Cloning in general
• GPCRs