Within the framework of a collaborative research center on
"Cellular membrane remodeling ",
the group of Dr. Anne Schlaitz at the Biochemistry Center of Heidelberg University (BZH) is offering a position for a Ph.D. student for the project:
"Creating shape and functions in the endoplasmic reticulum".
Ph.D. student position in molecular cell biology (m/f/d)
Activities and responsibilities
Project Description
Background The endoplasmic reticulum is a membrane-bound organelle crucial for cellular organization. Importantly, the endoplasmic reticulum forms the nuclear envelope that encloses chromatin, is the starting point for synthesis of secreted proteins, generates diverse cellular lipids and communicates with many other cell compartments through membrane contact sites. To fulfill all these functions, the endoplasmic reticulum assumes a unique architecture: it forms a single continuous membrane network that extends throughout the entire cell. This network consists of flat membrane sacks (called sheets) and highly curved membrane tubes (called tubules), which dynamically move and interconvert. Several specialized structures form in the endoplasmic reticulum, for instance nanoholes that perforate the sheets and membrane contact sites with other organelles. Distinct cell types organize their endoplasmic reticulum according to their biosynthetic needs with, for instance, secretory cells possessing many tightly packed sheets and lipid hormone-producing cells containing large amounts of tubular endoplasmic reticulum. In addition, diseased cells show altered endoplasmic reticulum organization and some pathogens, for instance viruses such as SARS-COV2, manipulate endoplasmic reticulum structure. Therefore, to understand how endoplasmic reticulum architecture correlates with the organelle's functions and to explore endoplasmic reticulum morphology for therapeutical purposes, we need to understand how endoplasmic reticulum structure is established.
Thesis project This project will build on our recent work on membrane shaping proteins of the REEP and Reticulon families, which create high curvature in the endoplasmic reticulum. The project and position will be embedded in the collaborative research center “Cellular membrane remodeling - how changing form creates function”, providing many opportunities for scientific collaborations, networking and mentoring.
Our biological model are human cultured cells and we employ a variety of cell culture techniques including CRISPR/Cas-mediated genome engineering. To analyze the specific functions of REEPs and Reticulons, we will perform co-immunoprecipitations and proximity-dependent biotin-identification (BioID) experiments and study the lipid environment of these proteins. For functional analyses, we use a broad range of molecular cell biology methods, in particular quantitative high-resolution and super-resolution light microscopy as well as volume electron microscopy. In the framework of the collaborative research center, we will complement our experimental results with molecular dynamics simulations and will contribute to an investigation on membrane remodelling by SARS-COV2.
Further reading
1. Golchoubian B, Brunner A, Bragulat-Teixidor H, Neuner A, Akarlar BA, Ozlu N, Schlaitz AL (2022) Reticulon-like REEP4 at the inner nuclear membrane promotes nuclear pore complex formation. J Cell Biol 221:e202101049.
2. Kumar D, Golchoubian B, Belevich I, Jokitalo E, Schlaitz AL (2019) REEP3 and REEP4 determine the tubular morphology of the endoplasmic reticulum during mitosis. Mol Biol Cell 30:1377-1389.
3. Schlaitz AL, Thompson J, Wong CC, Yates JR, 3rd, Heald R (2013) REEP3/4 ensure endoplasmic reticulum clearance from metaphase chromatin and proper nuclear envelope architecture. Dev Cell 26:315-323.
Methods that will be used:
cell culture including genome editing; quantitative microscopy including live and superresolution fluorescent light microscopy and volume electron microscopy; protein and lipid biochemistry methods such as co-immunoprecipitation, biotin identification, studies using functionalized lipids
Qualification profile
Profile of candidate’s qualification:
We are looking for a student who is keen to investigate fundamental cell biological questions related to the morphogenesis and organization of membrane-bound organelles. Candidates should have a background in molecular cell biology, biochemistry or related fields, be passionate about experimental research, enjoy working in an international team and be comfortable communicating in English.
We offer
At Heidelberg University you will find cutting edge research and a highly collaborative and friendly atmosphere in an international, open-minded environment.
Payment will be according to the German TVL pay scale (TVL13, 65%). Start of the PhD project should be between August and November 2024.
Please refer to our website for further information:
https://www.bzh.uni-heidelberg.de/schlaitz/
Please contact Anne Schlaitz directly in case of questions.
Please send your application including a cover letter, CV and contact information of two referees via
email