Molecular biology, Molecular genetics or Molecular medicine – PhD position with stipend “Molecular and physiological mechanisms in anion-exchanger AE3-medicated regulation of the QT-interval”, at the Department of Molecular Biology and Genetics, Aarhus University, Denmark
Deadline to Apply
May 15, 2021 (23: 59 GMT +1)
|No. of Position(s)||1|
|Research Area||– Molecular biology|
– Molecular genetics
– Molecular medicine
|Scholarship||According to standard norms|
|Workplace||Department of Molecular Biology and Genetics|
Department of Cardiology
Aarhus University Hospital
|Contract Period||Not specified|
|Starting date||Aug 01, 2021|
- You hold – or soon graduate with – a Master’s degree within molecular biology, molecular genetics or molecular medicine.
- Experience with basic molecular biology lab work is required.
- Experience with CRISPR/CAS9 technique is advantageous but not required.
- Experience with zebrafish work is advantageous but not required.
- Completed course in laboratory animal science (FELASA) is advantageous.
- Knowledge about or strong interest in molecular medicine is advantageous.
- Knowledge about experimental cardiac physiology methodology is advantageous.
- You enjoy working in a team and can communicate easily with different people.
- You understand deadlines and are goal oriented.
- Proficiency in both oral and written English is required.
We have discovered that the cardiac chloride-bicarbonate exchanger AE3 is involved in the development of inherited heart disease. Our discovery, published in Nature Communications 2017, adds another gene (SLC4A3) and a new disease mechanism for the development of Short QT Syndrome (SQTS). Our study showed that cardiomyocytes with SQTS-associated AE3 mutation have a reduced chloride-bicarbonate-exchange activity. This results in increased pHi and decreased [Cl-]i, which likely causes shortening of action potential duration and ventricular arrhythmia.
As a continuation of this novel finding, we have expanded our studies in a large SQTS patient population with clinical-genetic analysis and experimental characterization of novel SLC4A3 variants in our zebrafish embryo model.
Altered anion transport is a novel genetically-induced mechanism for development of fatal arrhythmia and may provide new therapeutic possibilities not only in SQTS but also other types of arrhythmias detected in patients carrying AE3 variants with normal and prolonged QT-intervals. It opens the door to an entirely new field to be further investigated both clinically and experimentally.
You will be a member of “Genomic Cardiology”, an established research group at the Department of Cardiology, Aarhus University Hospital headed by Prof. Henrik Kjærulf Jensen, which operates at the intersection between clinical cardiology, molecular genetics, experimental cardiac physiology and genomics.
In this PhD position, you will at the Department of Molecular Biology and Genetics, AU (Kasper Kjær-Sørensen, PhD and Prof. Claus Oxvig) create an optimized zebrafish model that will facilitate further investigations of novel AE3 variants identified in the heart patients with altered QT-intervals, ventricular tachyarrhythmias, and sudden cardiac death. Using CRISPR/Cas9 and other relevant technologies, you will generate AE3 knockout and knockin zebrafish as well as transgenic zebrafish lines allowing for optical recordings of relevant physiological parameters in vivo.
Together with our collaborators at the Department of Biomedicine, Health, AU (Ass. Prof. Vladimir Matchkov and Prof. Christian Aalkjær) we will apply the developed zebrafish embryo model to explore molecular and physiological mechanisms of AE3-mediated regulation of the QT-interval including measurements of cardiac pHi, Ca2+-uptake and ECG.
You will be working at the Department of Molecular Biology and Genetics and the Department of Biomedicine, AU under supervision of Kasper Kjær-Sørensen, PhD, Prof. Claus Oxvig, Ass. Prof. Vladimir Matchkov, and Prof. Christian Aalkjær.
Together with the Department of Clinical Medicine, Health, AU, this triad of departments offers a vibrant and unique interdisciplinary research environment within experimental and translational molecular cardiology research powered by genomics. You will also be supervised by Prof. Henrik Kjærulf Jensen, who will act as your formal PhD supervisor together with Ass. Prof. Vladimir Matchkov and Prof. Claus Oxvig.
How to Apply?
To apply, please click the Apply Online mentioned above
For information about application requirements and mandatory attachments, please see our application guide.
Clinical professor Henrik Kjærulf Jensen
Post expires at 8:59am on Sunday May 16th, 2021 (GMT+9)