Im Institut für Molekulare und Zelluläre Anatomie der Uniklinik RWTH Aachen sind zum frühestmöglichen Zeitpunkt folgende Stellen zu besetzen:
The Institute for Molecular and Cellular Anatomy (MOCA) is seeking a
PhD student (m/f/d)
for the project Stress-protective properties of intermediate filaments in the intestinal epithelium of Caenorhabditis elegans.
The position is open starting as soon as possible. The compensation will be according to German EG 13 TV-L for 65% and one year with option of extension.
Epithelia delimit the body against the surrounding environment. They serve as barriers that allow selective molecule exchange. Cell-cell adhesion complexes are essential for maintaining the barrier. The function of the different types of associated filaments, which link the adhesion sites to the cytoskeleton, is currently not understood.
The aim of this project is to find out how the linkage between adhesion sites and the intermediate filament cytoskeleton affects the protective barrier in the intestine. The nematode Caenorhabditis elegans will be used as a model, because it presents a unique distribution and composition of its intermediate filament cytoskeleton in all of its 20 intestinal cells. The intestinal intermediate filaments, which are composed of 6 different polypeptide subunits, are anchored at the C. elegans apical junction and are enriched below the intestinal lumen. Initial experiments support our working hypothesis that the intestinal intermediate filament cytoskeleton protects against different types of stress (Geisler et al., 2016, 2019, 2020).
- Generate reporter strains using Crispr to study the distribution and dynamics of fluorescently-labelled intermediate filaments in vivo with different microscopic setups (apotome, confocal microscopy with Airy Scan, lightsheet) Generate intermediate filament knockouts to examine consequences on intestinal anatomy and function using different light and electron microscopic techniques
- Investigate the stress sensitivity of intermediate filament knockouts using confrontation assays with pathogenic bacteria, bacterial toxins and hyperosmotic / oxidative environments
- Generate and analyze knockout animals lacking multiple intermediate filament subunits
The successful candidate will elucidate
- how the targeted knockout of individual intestinal intermediate filament subunits affects intermediate filament network formation and stress-resilience in the intestine,
- whether the loss of multiple intermediate filament subunits elicits additive effects on the morphology, function and stress resilience of the intestinal epithelium, and
- to which degree the intermediate filament network contributes to the overall intestinal barrier function in different stress paradigms.
The results will have direct implications on the situation in vertebrates, which have a comparable organization of their intermediate filament system and corresponding adhesion sites in the intestine.
We are seeking applicants who have completed a diploma or master's degree in biology or a related life science field, who have experience in molecular biological techniques, microscopic examination methods and in working with model organisms, and are interested in cell biological questions. Independent work is expected and a PhD should be sought.
Further information can be found at www.moca.rwth-aachen.de.
The RWTH Aachen University is certified as a family-friendly university and offers a dual career program for partner hiring. We particularly welcome and encourage applications from women, disabled people and ethnic minority groups, recognizing they are underrepresented across RWTH Aachen University. The principles of fair and open competition apply and appointments will be made on merit.
Please send your application including names and contact data of two referees by 06.12.2020 naming the reference code GB-P 26095 to Mr. Dr. Florian Geisler, Institute of Molecular and Cellular Anatomy, Wendlingweg 2, RWTH Aachen, D- 52057 Aachen.
For further information please contact Mr. Dr. Florian Geisler, Fon.: 0241-80 88927, E-Mail: fgeislerukaachende
We are currently seeking a highly motivated
medical student (f/m/d)
for a project on “Mechanobiology of genetically modified retinal epithelium”.
The integrity and homeostasis of the retinal pigment epithelium (RPE) are critical to sustain the healthy function of the retina. RPE cells tightly interact with each other, forming a monolayer of cuboidal and polarized cells located between the choriocapillaris and the photoreceptor outer segments. It fulfils multiple tasks, including the maintenance of the blood-retina barrier to protect the retina, the transport of nutrients, the removal of metabolic products and the secretion of vital factors and molecules. Degeneration of the RPE interferes with the normal retinal metabolism, breaks the blood-retina barrier and causes vision loss. The RPE undergoes chronic mechanical stress, which generally plays a critical role in the (patho-)physiology of living cells. Dysfunctions contribute to the pathogenesis of many retinal degenerative diseases, such as proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), RPE tears and high myopia. These diseases have global prevalences of up to 3% and are characterized by harmful stretching of the RPE, resulting in the distortion of the retinal architecture up to retinal detachment and leading to the disruption of the essential interactions between RPE and outer retina and, finally, to blindness.
This project aims to characterize the mechanobiology of genetically modified retinal pigment epithelium. The genes for pigment epithelium-derived factor (PEDF) and brain-derived neurotrophic factor (BDNF) are delivered via electroporation using the Sleeping Beauty transposon system. The functionality of the monolayers from non-transfected and transfected cells will be performed by electrical impedance spectroscopy to monitor RPE barrier properties and morphological changes, as well as traction force microscopy and monolayer stress microscopy to evaluate RPE mechanobiological properties.
The resulting characterization of the genetically modified monolayers will set a step forward for the use of the transfection strategy in a novel therapeutic strategies.
• Optimization of traction force microscopy and electrical impedance spectroscopy of RPE.
• Live imaging of RPE monolayer’s actin cytoskeleton with confocal microscopy
• Computational data analyses using MATLAB and Fiji software
• You are studying medicine
• You are interested in the field of mechanobiology
• You are interested in mammalian cell culture
• You are a reliable and careful worker with the ability of integrating well in a team
The student will have the possibility to apply for a scholarship to the German Society of Ophthalmology and will be working in a team of engineers, physicists, biologists and medical doctors from the groups of Dr. Di Russo (UKA, DWI), Dr. Johnen (UKA) and Dr. Linkhorst (RWTH).
If you are interested, please contact Dr. Jacopo Di Russo at jdirussoukaachende.