PhD position in Life Sciences

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.

Activities and responsibilities

Studying the mechanisms and regulation of the Sec61-mediated Ca2+ leakage from ER.

Qualification profile

MSc or an equivalent qualification in Biology, Biochemistry, Biophysics, Physiology, Immunology, Pharmacy or a closely related discipline.

Benefits

For details, please visit the homepage of the Collaborative Research Center SFB 894 (http://sfb894.uni-saarland.de/start).

Send application to

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.
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.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 http://sfb894.uni-saarland.de/start.

While applying for the job please refer to jobvector and use the following reference number: JVSL_0419

About Universität des Saalandes

Das übergeordnete Thema der Arbeitsgruppe sind Mechanismen der Proteinbiosynthese. Unter diesem Oberbegriff werden die Mechanismen der intrazellulären Proteinfaltung sowie Mechanismen des intrazellulären Proteintransports untersucht. In Hinblick auf Proteintransport werden Mechanismen des Imports von Proteinen in das endoplasmatische Retikulum bzw. in den Zellkern sowie...

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