In this publication (PI: Bernd Schroeder) the expression and function of the orphan intra-membrane protease SPPL2c was systematically analysed. SPPL2c is an ER-resident protein, which is specifically expressed in murine and human testis under endogenous conditions. There, it is present in developing germ cells with the highest abundance in spermatids. Consequently, differentiation and function of male germ cells are compromised in SPPL2c-deficient mice. SPPL2c exhibits proteolytic activity. Similar to SPP, SPPL2c cleaves selected tail anchored proteins,
however with a distinct, only partially overlapping substrate spectrum. Using proteomics, we have identified the SERCA regulating protein phospholamban (PLN) as physiological substrate of SPPL2c, presumably leading to a dysregulation of intracellular Ca2+ handling in SPPL2c KO male germ cells.

Reading:

Niemeyer, J., Mentrup, T., Heidasch, R., Mueller, S., Biswas, U., Meyer, R., Papadopoulou, A., Dederer, V., Haug-Kroeper, M., Adamski,V., Lüllmann-Rauch, R., Bergmann, M., Mayerhofer, A., Saftig, P., Wennemuth, G., Jessberger, R., Fluhrer, R., Lichtenthaler,S., Lemberg, M., Schröder, B. (2019)
The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban.
EMBO Reports, in press

The Biochemical Institute as part of the Medical Faculty at the Christian Albrechts- University Kiel (Germany) has an opening for

Research assistant
(at the doctoral dissertation level)

in the Department of Molecular Cell Biology and Transgenic Biology (Prof. Dr. P. Saftig) from March 15th 2019 until June, 30, 2022 to do research in the field of protease research as part of the collaborative research center 877. The position is paid according to E 13 TV-L. The regular weekly working hours amount to 65 % of a full time position (currently 25,155 hours).

The position is available to study the role of the metalloproteinase ADAM10, its cell biology and its regulation. Our previous studies have contributed to the view that the metalloproteinase ADAM10 has emerged as one of the most fascinating proteases, with crucial functions in development, tissue physiology and disease. We could reveal ADAM10´s role in leukocyte migration, axon targeting, glia and synapse function and in developmental processes as a sheddase for Notch receptors and cadherins. In a disease context we could show that ADAM10 plays major roles in atherosclerosis, liver and kidney disease and in neurodegeneration as a prion disease modulator. We could demonstrate that the intracellular trafficking, maturation and half-life of ADAM10 is regulated by certain tetraspanins, which can associate in larger protease-substrate complexes. Selection of our recent review articles related to our work on ADAM10 and tetraspanins: Saftig & Lichtenthaler , Progr. Neurobiol. 2015; Seipold & Saftig, Front. Mol. Neurosci. 2016; Wetzel et al. Biochim Biophys Acta. 2017.

We seek enthusiastic, highly motivated people with a University master degree or diploma to join our international research group. The projects involve the analysis of genetic mouse models, cell-based assays, microscopy, molecular biology and histology techniques. Previous experience in these methodologies and a background in molecular biology, cell biology, biochemistry or immunology is provided.

The University of Kiel strives to increase the proportion of female researchers in research and teaching and therefore calls upon qualified women to apply. Women are given priority in the case of equivalent qualifications, proficiency and professional performance. The University of Kiel has an equal opportunities policy for persons with recognized disabilities. Disabled persons with the necessary qualifications will therefore be given priority. Applications by people with a migration background are particularly welcomed.

Please refrain from submitting application photos. Applicants are requested to send a statement of interest, a full CV incl. certificates as names and addresses of at least two references in a single pdf file (deadline: February 25th, 2019) to:

Prof. Dr. Paul Saftig
Biochemisches Institut der CAU Kiel
Olshausenstr. 40
D-24098 Kiel, Germany
E-Mail: psaftig@biochem.uni-kiel.de
Tel.: ++49-(0)431-8802216
Fax: ++49-(0)431-8802238
https://www.uni-kiel.de/Biochemie/saftig

Lysosomal storage disorders – challenges, concepts and avenues for therapy: beyond rare diseases

This Review aims to discuss how lysosomal storage affects functions linked to lysosomes, such as
membrane repair, autophagy, exocytosis, lipid homeostasis, signalling cascades and cell viability. Therapies must aim to correct lysosomal storage not only morphologically, but reverse its (patho)biochemical consequences. As different LSDs have different molecular causes, this requires custom tailoring of therapies. We will discuss the major advantages and drawbacks of current and possible future therapies for LSDs. Study of the pathological molecular mechanisms underlying these ‘experiments of nature’ often yields information that is relevant for other conditions found in the general population. Therefore, more common diseases may profit from a correction of impaired lysosomal function.


André R. A. Marques, Paul Saftig
J Cell Sci 2019 132: jcs221739 doi: 10.1242/jcs.221739 Published 16 January 2019