Open positions at MOCA

We are currently seeking a

PhD Candidate (m/f/d)

Title: Establishment of an organoid model to study ECM contribution to retinal mechanobiology
at the Interdisciplinary Centre for Clinical Research (IZKF) and DWI Leibniz-Institute for Interactive Materials.

Project Description:
Retinal degeneration pathologies, such as age-related macular degeneration (AMD), are the major cause of sight loss worldwide. Besides genetic causes to date little is known about the aetiology of the diseases, being the reason for the lack of efficient treatments. This is due to the limited availability and flexibility of research models which can fully recapitulate the retina system. Particularly understudied is the role of extracellular matrices (ECM) in maintaining a healthy and functional retinal pigment epithelium (RPE) and its interaction with the light-detecting photoreceptors cells. RPE is localized at the base of the neural retina and tightly adheres to the underlying basement membrane (BM), which constitutes the proximal part of the Bruch’s membrane. While the BM components carry the biochemical information for RPE adhesion, deeper layers of the BrM, composed of fibrillar collagens and elastin fibres, are proposed to determine RPE physical properties. Furthermore, health, stability, and adhesion of the neural retina to the RPE layer strongly depend on the hyaluronic acid-rich interphotoreceptor matrix.  
The PhD project aims to establish an organoid model to study the role of ECM on retinal mechanobiology. The candidate will work in engineering a novel system combining current state-of-the-art human retinal organoids with light and magnetic tunable anisotropic hydrogels.  
While animal studies, genome analyses, and patient tissue biopsies have until now only contributed to the understanding of the general function of ECM in retina physiology and pathology, the development of a novel in vitro model will provide new insights into the contribution of molecular and structural components of the ECM the biology of RPE and its functional interaction with the neural retina.

We offer:
We offer close supervision with the aim of supporting a highly-skilled, independent scientist in the field of mechanobiology. The candidate will have the possibility to learn state-of-the-art techniques varying from material science to chemistry and biology. The PhD will be carried out in a highly interdisciplinary environment at the RWTH Aachen University and DWI Leibniz-Institute for Interactive Materials. Furthermore, the student will have the possibility to be associated with the mechanobiology graduate school ME3T (me3t.rwth-aachen.de).
The successful candidate will receive a contract with a salary corresponding to 65% of the level 13 TV-L German public system. The position is available starting immediately.
For more information about our research, please visit the group webpage: dirusso.rwth-aachen.de.

Your skills and qualifications:
The candidate should hold a Master of Science in bioengineering, cell and molecular biology, or related disciplines. Sound knowledge of stem cell culture is a plus. Candidates should show a keen interest in working in an interdisciplinary environment that IZKF, RWTH Aachen and DWI offer.

To apply, please send by email a brief description of your research interests, curriculum vitae and the names of two academic referees to Dr. Jacopo Di Russo (jdirussoukaachende)

Application Deadline: 15.08.2022

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We are currently seeking a highly motivated

life science student (f/m/d) for a master thesis on

“Mechanical homeostasis of retinal pigment epithelium in ageing”

Age-related macular degeneration is the most impactful blinding disease of the elderly population. The most vulnerable outer retinal layer involved in AMD pathogenesis is the retinal pigment epithelium (RPE). RPE cells experience severe remodelling during the disease - alterations of their extracellular matrix, cellular hypertrophy, increased size heterogeneity and severe cytoskeletal remodelling. These alterations strongly suggest changes in epithelial mechanics. With age being the major risk factor for AMD, it is crucial to understand how the healthy RPE ages in terms of mechanics to identify when a phenotypic switch may lead to AMD.
The RPE is a post-mitotic epithelium, meaning cells cannot proliferate in response to apoptosis. Cellular hypertrophy and reconfiguration compensate for the linear reduction of RPE cell numbers with age. The induction of apoptosis in vitro can mimic RPE ageing and provide the opportunity to ‘mechanically age’ the epithelial monolayer similarly to material ageing. It is unknown if this age-related density reduction affects monolayer mechanics of the RPE and what implications the effects have on RPE function.

Project aim:

The project aims to characterise epithelial mechanics of an ageing post-mitotic epithelium. Ageing of hiPSCs-derived RPE cells will be mimicked by inducing large-scale density reduction. At the same time, mechanics will be analysed in terms of traction forces, stresses within the monolayer, cell stiffness and monolayer arrangement. 

If you are interested, please send a short motivational letter, CV and transcripts at jdirussoukaachende

We offer:

• Interdisciplinary and active research environment
• Close practical and theoretical supervision
• Possibility for ending up in publication

Your tasks:

• Culture of hiPSCs-derived RPE on polyacrylamide hydrogels and ageing-mimicking stimulation
• Traction force and monolayer stress microscopy of ‘aged’ vs control cells
• Segmentation and image analysis
• Optional: Nanoindentation, immunofluorescent staining

Your profile:

• Master student in Biology, Biotechnology, Biomedical engineering, or a related discipline
• Motivated, focused and team-oriented attitude
• Experience with cell culture, microscopy, AFM, Fiji or Matlab are a plus

If you are interested, please send a short motivational letter, CV and transcripts at jdirussoukaachende.

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We are currently seeking a highly motivated

Master student (f/m/d)

for a project on “ Regulation of cardiogenesis in desmosome deficient mouse embryos”.

Desmosomes are important structural junctions between cardiomyocytes that maintain cellular structure and confer tissue integrity. In the “Heart research group” of MOCA we aim to study the impact of mutations in desmosomal proteins during early heart morphogenesis. To this end, transgenic animal models will be utilized to investigate in vivo cardiogenesis under specific genetic conditions. In the first phase of the project, desmosome formation will be compared in different transgenic animals to wild type controls. In the second phase of the project cardiomyocytes shape, cytoarchitechture and their extracellular matrix composition will be studied.

Your Tasks

• Histological analysis of embryonic heart, including tissue fixation, sectioning by microtome and staining of the tissue slides
• Detection of protein expression and localization using immunohistochemical techniques
• Visualizing protein expression and localization by fluorescence microscopy and analyzing data via ImageJ software.
• Analysis of RNA expression and localization via in situ hybridization techniques

Your profile

• B.Sc. in biology, biomedical  or related studies
• Interested in developmental aspects of heart
• Previous lab experiences is a plus but not required
• Detail oriented, a good observer, and well organized

**Funding is available to support the student as a HIWI.

Please send your application including your CV, cover letter and transcripts to Mrs. Dr. Hoda Moazzen, hmoazzenukaachende.

Institute of Molecular and Cellular Anatomy
RWTH Aachen University

Wendlingweg 2
D-52057 Aachen
Phone: +49 (0) 241 80 85298
Email: hmoazzenukaachende
Web:  https://www.moca.rwth-aachen.de/heart_disease.html

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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.

Your Tasks

•    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

Your profile

•    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.

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We are currently seeking a highly motivated

Master student (f/m/d)

for a project on “Systematic characterization of cytoskeletal proteins of the human endometrium”.

The inner uterine wall (the so-called endometrium) undergoes hormone-driven cyclic changes to allow the embryo to implant; during the “window of implantation” on cycle days 19-23 the cell-cell junctions of endometrial cells remodel and only then the endometrium becomes receptive for the blastocyst. However, there are hardly any studies that look at these changes systematically. Through close cooperation with a fertility clinic, our institute has numerous endometrial biopsies. This allows us to characterize inter- and intraindividual cell morphological differences for the first time. This knowledge will contribute to a better understanding of the causes of involuntary childlessness.

Your Tasks

The goal of this thesis is the systematic characterization of relevant cytoskeletal proteins in the human endometrium during the „window of implantation“. You will learn how to embed human tissue in paraffin, slice it using a microtome, and label target structures by immunohistochemical techniques. Using modern microscopy techniques, you will learn how to detect, evaluate, and present antibody-labeled structures.

What we offer

• A defined project that combines classical biomedical research methods with the clinics
• Working in a methodically broadly based research institute and integration into the interdisciplinary grad school “Mechanobiology in 3D Epithelial Tissues (ME3T)“
• Direct supervision with a high level of technical expertise in histology and microscopy
• The possibility to bring in own ideas
• Flexible start date and own office workstation

If you are interested, please contact Anna Sternberg, M.Sc., at asternbergkaachende.

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We are currently seeking an enthusiastic

Master student (f/m/d) or Medical student (f/m/d)

for a project on the “Characterization of the cytoskeletal-mitochondrial crosstalk”

The cytoskeleton is composed of three distinct networks: actin, microtubules and intermediate filaments. Despite their major function in providing stability and resilience to cells, intermediate filaments have been shown to influence a variety of other cellular processes including the localization and function of mitochondria.

We have previously shown that keratin intermediate filaments interact with components of the mitochondrial motility complex. Now we aim to characterize this crosstalk.

Your tasks

• Cloning of mutants of keratin intermediate filaments
• Live cell imaging of transfected epithelial cells using confocal microscopy
• Image analysis using Fiji software

Your profile

• You are a Master student in Biology, Biotechnology or a related discipline

or

• You study medicine and want to start after your “Basisprüfung”
• You are reliable and highly organized.

If you are interested, please send a short motivational letter and CV to Dr. Nicole Schwarz at nschwarz@ukaachen.de

Further reading: https://pubmed.ncbi.nlm.nih.gov/27399781/

We are currently seeking an enthusiastic

Master student (f/m/d) or Medical student (f/m/d)

for a project on the “Characterization of the keratin dependent organelle organization”

The cytoskeleton is composed of three distinct networks: actin, microtubules and intermediate filaments. Despite their major function in providing stability and resilience to cells, intermediate filaments have been shown to influence a variety of other cellular processes including the localization and function of different organelles.

We have previously shown that keratin intermediate filaments interact with mitochondria. Now we aim to characterize the consequence of intermediate filament loss or mutation on the localization and organization of other organelles such as Golgi and ER.

Your tasks

• Micropatterning
• Cell culture of patient derived keratinocytes
• Fluorescence microscopy
• Image analysis using Fiji software

Your profile

• You are a Master student in Biology, Biotechnology or a related discipline

or

• You study medicine and want to start after your “Basisprüfung”
• You are reliable and highly organized.

If you are interested, please send a short motivational letter and CV to Dr. Nicole Schwarz at nschwarz@ukaachen.de

Further reading: https://pubmed.ncbi.nlm.nih.gov/27399781/

We are currently seeking an enthusiastic

Master student (f/m/d) or Medical student (f/m/d)

for a project on the “Characterization of two distinct keratin subnetworks”

The cytoskeleton is composed of three distinct networks: actin, microtubules and intermediate filaments. Together with cell-cell contacts and cell-matrix-contacts keratin intermediate filaments provide stability and mechanical resilience to epithelial cells.

We have previously shown that the keratin intermediate filament network can be further subdivided into distinct subnetworks; one that connects the nucleus to the periphery and one that lies underneath the plasma membrane and interconnects cell-cell-contacts. To further investigate the role of this subdivision we recently established keratin mutants that we aim to mechanobiologically characterize in this project.

Your tasks

• Live cell imaging and FRAP of transfected epithelial cells using confocal microscopy
• Mechanobiological assays (NanoIndentation and Traction force microscopy)
• Image analysis

Your profile

• You are a Master student in Biology, Biotechnology or a related discipline

or

• You study medicine and want to start after your “Basisprüfung”
• You are reliable and highly organized.

If you are interested, please send a short motivational letter and CV to Dr. Nicole Schwarz at nschwarz@ukaachen.de

Further reading: https://pubmed.ncbi.nlm.nih.gov/29032358/