The MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE (MDC) is a member of the Helmholtz Association of National Research Centers, supported by the Federal Government of Germany and the Land Berlin.
we are looking for one PhD student position.
New mechanisms regulating the old L-type Ca2+ channel L-type voltage dependent Ca2+ channels (L-VDCCs; CaV1.2), crucial in cardiovascular physiology and pathology, are modulated via activation of G-protein-coupled receptors and protein kinase A (PKA) and C (PKC). Although the mechanisms of these modulations have been studied extensively, still many unsolved questions remain, and specific pharmacological tools to target such regulations are lacking. Our preliminary work suggests complex regulatory mechanisms and activation of distinct PKA- and PKC-induced signaling pathways that involve further regulatory proteins such as A-kinase anchoring proteins (AKAPs). CaV1.2 undergoes post-translational modifications yielding full-length channels, and, due to proteolytic cleavage, C-terminally truncated forms and N-terminal fragments. The extent to which CaV1.2 channels are cleaved in different tissues, and the effect of truncation on channel modulation by transmitters and hormones remain to be determined. We hypothesize that the mechanisms by which PKA enhances activity of CaV1.2 involves N- and C terminal fragments.
The specific aims of the proposed PhD thesis are:
1. Elucidation of the molecular mechanism of PKA regulation of CaV1.2 with the focus on newly discovered roles of N- and C-terminal fragments of the channel.
2. Identification of AKAPs specifically linked to PKA regulation of CaV1.2.
3. Develop novel peptidic and non-peptidic substances that interfere with direct protein-protein interactions of CaV1.2 to interfere with its β-adrenergic regulation: as tools and as putative starting points for the development of anti-heart failure drugs. The project involves a variety of cutting edge technologies such as electrophysiology, FRET imaging in cells, characterizing protein-protein interaction, small molecule and peptide library screening. The outlined study will contribute to understanding the diverse mechanisms of modulation of cardiac CaV1.2 by PKA, and will provide novel tools for their study, and may also pave the way to novel concepts for the treatment of human cardiac diseases such as heart failure. The project will be in very close collaboration with Prof. Nathan Dascal, Tel Aviv University, Israel. Visits and/or secondments in his lab are planned.
Talented and enthusiastic student with a strong interest in life sciences and a strong background in biochemistry and cell biology. The candidate must be highly motivated. You should hold or expect to obtain a Master degree or German diploma not later than January 2019. We accept applications from students with degrees in biology, molecular medicine or related subjects such as pharmacy. The working language is English.
Salary: TVöD/Bund E13 (50% first year, 65% afterwards)
The position is initially limited to 3 years.
Earliest start date is January 2019.
For further information please contact:
If you have questions don’t hesitate to write to Enno.firstname.lastname@example.org.
As we seek to increase the number of women in computational disciplines, we explicitly encourage women to apply. We are an equal opportunity employer and value diversity at our institution.
The MDC is an equal opportunity employer and supports gender equality. Please, send your application including all documents indicating the registration number 10993/2018 until October 31, 2018 preferably by e-mail to: email@example.com as pdf files (2 files of 5 MB at the maximum) as we do not return any papers.