Vacancies

April 9, 2019

Within the SFB 894 Ca2+ signals: Molecular Mechanisms and Integrative Functions, the following PhD position is available in the lab of Dr. Sven Lang (Medical Biochemistry and Molecular Biology) and Prof. Dr. Adolfo Cavalié (Experimentelle und Klinische Pharmakologie und Toxikologie) at the Faculty of Medicine, Saarland University, Homburg:

Mechanisms and regulation of the Sec61-mediated Ca2+ leakage from the ER
In mammalian cells a large volume of the cytoplasm is occupied by a tubular network called the endoplasmic reticulum (ER). Within the ER membrane resides the pore-forming Sec61 complex which mediates the translocation of most precursor proteins entering the ER and the efflux of calcium from the ER. Thus, the Sec61 complex is intimately linked to protein biogenesis and calcium signaling (Lang et al. 2017). Aside from the mechanistic details of the Sec61-mediated protein and calcium flux our labs address regulation of the Sec61 complex by accompanying partner proteins as well as pharmacological modulation by small molecules (Nguyen et al. 2018, Gamayun et al. 2019). In addition, our recent work led to the identification of the first, active ATP transporter of the mammalian ER membrane (Klein et al. 2018).

To study the intricate functions of the Sec61 complex our labs use a multitude of assays and techniques. We investigate the transport of soluble and membrane proteins using a reconstituted assay combining cellular ER fractions and in vitro synthesis of radioactively labeled precursor proteins. Membrane translocation or integration is visualized by specific ER-limited posttranslational modifications (Dudek et al. 2013). Live-cell imaging employing compartmentalized sensors such as FURA-2 or genetically encoded probes like GCaMP-150 and ERAT4.01 is the method of choice to address calcium and ATP flux across the ER membrane, respectively. We routinely combine such sensors with siRNA mediated gene silencing and genetic complementation for different targets of interest including the Sec61 complex (Lang et al. 2011). Furthermore, with the increasing number of disease-associated variants our characterization of Sec61-mediated processes addresses the underlying patho-mechanisms of various disease-relevant alleles in cellular model systems or mouse-tissues. Our efforts are further supplemented by employing a medium-throughput screening platform for cellular calcium flux measurements addressing the impact of small molecules on calcium homeostasis.

We invite applications from highly qualified and motivated students of any nationality, who are interested in studying the mechanisms and regulation of the Sec61-mediated Ca2+ leakage from ER. We are looking forward to your application. The funding covers a period of 3.5 years starting from August 2019. For further information don’t hesitate to contact us (sven.lang@uni-saarland.de or adolfo.cavalie@uks.eu) or go to sfb894.uni-saarland.de/start.

December 12, 2018

In the lab of Prof. Dr. Veit Flockerzi in Homburg, several positions for PhD students are available with immedeate effect:

1.-3.: The Cavbeta3 protein as a pharmacological target to accelerate wound healing, to increase bone mineralization and to tighten the blood-brain barrier

The absence of the beta 3 protein of voltage-dependent calcium channels (Cavbeta3) affects bone mineralization, skin wound healing and blood-brain barrier tightness. In order to further investigate these effects and to identify possible pharmacological therapies, the following three positions for doctoral students are available:

1. Role of Cavbeta3 protein for bone mineralization and fracture healing.
2. Role of Cavbeta3 protein for wound healing of the skin.
3. Role of the Cavbeta3 protein for the tightness of the blood-brain barrier with respect to neuro-inflammatory processes.

The aim is to accelerate wound healing, to improve bone mineralization and to reduce the risk of neuro-inflammatory processes.

Literature
Belkacemi et al. (2018), Cell Reports 22: 1339-1349
Jha at al. (2009) Nature Immunology 10: 1275-1282
Berggren et al. (2004) Cell 119: 273-284

4. The function and pharmacological properties of the ‘calcium channel flower domain-containing protein 1’ (Cacfd1) in brain capillary endothelial cells

The 'calcium channel flower domain-containing protein 1' is involved in calcium-dependent endocytosis at contact sites of the plasma membrane with membranes of subcellular organelles. The aim is to characterize the functions of Cacfd1 in vascular endothelial cells with regard to vascular permeability and to identify its pharmacological susceptibility.

Literature
Chang et al. (2018), Journal Cell Biology 217: 667-683

5.The function and pharmacological properties of the ‘transient receptor potential canonical 1’ (TRPC1) channel in the liver

Within this project, the function of the TRPC1 protein and its influence on detoxification reactions will be investigated in the liver. The aim is to characterize TRPC1 as a target molecule for pharmacological treatment of liver failure.

Literature:
Flockerzi & Nilius (2014) (eds), Mammalian Transient Receptor Potential (TRP) Cation Channels Vol. 1 6 Vol. 2, Handbook of Experimental Pharmacology 222 & 223, Springer-Verlag Berlin Heidelberg 2014.

For all projects, the following methods are required:
Molecular pharmacological methods, transgenic techniques, imaging and electrophysiology, high-resolution mass spectrometry, genetic visualization and manipulation of cells.

Mandatory conditions for employment are:
MSc or an equivalent qualification in Biology, Biochemistry, Biophysics, Physiology, Immunology, Pharmacy or a closely related discipline.

Physically handicapped persons will be preferred in case equally qualified.

We aim to increase the number of women in this field. Therefore, women are encouraged to apply for this position.

We are looking forward to applications from highly qualified and motivated students of any nationality.

Send your application to:
Dr. Gabriele Amoroso
Department of Plant Physiology
Faculty of Biology
University of Kaiserslautern
Erwin-Schrödinger-Straße
D-67663 Kaiserslautern
gamoroso-noSpam-@rhrk.uni-kl-noSpam-.de

Please do not include original documents and certificates! Application papers will not be sent back. Please do not use binders.