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Wendt Lab

Department                            Cell Biology

Principal investigator          Kerstin Wendt

E-mail address                      k.wendt@erasmusmc.nl

Website                                     https://www.erasmusmc.nl/en/research/researchers/wendt-kerstin

 

Chromatin dynamics of chromatin regulators depending on cohesin and cohesin regulators

Suitable as a BEP? No

Suitable as a MEP? Yes

Suitable as an Academic Research Project? Yes

Techniques:

  • CRISPR
  • FRAP
  • Western blotting
  • Immunostaining
  • Chromatin immunoprecipitation

Depletion of cohesin or cohesin regulators leads to stalling of loop extrusion and other chromatin-related processes. This brings about changes in the portfolio of chromatin regulators that are associated with chromatin.
In this project we will investigate how the depletion of cohesin proteins changes the binding dynamics of selected chromatin regulators.
In this project you will investigate two selected proteins that show opposite behavior in our preliminary data. We will introduce Halo-tags at the proteins by genome editing and analyze the dynamics of the proteins by FRAP. In parallel, you will use other methods available in the lab to address the behavior of the proteins (western blotting, immunostaining, chromatin immunoprecipitation).

Further reading (click to link to article)

DOI: 10.1186/s13072-025-00598-2

Migration of Developing Neuronal Cells in Brain Organoids

Suitable as a BEP? Yes

Suitable as a MEP? Yes

Suitable as an Academic Research Project? No

Techniques:

  • Image segmentation
  • Object tracking
  • Potentially live cell imaging (MEP)

Cornelia de Lange syndrome is a developmental disorder causing intellectual disability and brain malformations due to NIPBL mutations. We use mixed dorsal forebrain organoids containing healthy and diseased cells to study neuronal development. Cells are labeled with mCherry or EGFP, and live imaging of organoid slices visualizes neuronal migration. You will analyze existing time-lapse movies to track individual cells and compare migratory behavior (e.g., speed, distance), optimizing image segmentation and tracking algorithms. The project can be a BEP or MEP; the MEP includes cell cultures and additional imaging. Work will be conducted in collaboration with the Debbie van den Berg group.

Further reading (click to link to article)

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Impact of an HDAC8 mutation in a patient

Suitable as a BEP? Yes

Suitable as a MEP? No

Suitable as an Academic Research Project? No

Techniques:

  • Cell culture
  • Western blotting
  • Immunostaining
  • Chromatin immunoprecipitation

HDAC8 deacetylates the cohesin subunit SMC3 after mitosis, allowing cohesin to recycle and rebind chromatin in the next cell cycle. Loss or mutation of HDAC8 causes accumulation of acetylated SMC3, defective sister chromatid cohesion, disrupted gene regulation, and developmental disorders resembling Cornelia de Lange syndrome.
In this project we will assess the enzymatic activity of an HDAC8 mutation hat was observed at a patient at the Erasmus MC. You will grow skin fibroblasts of the patient and controls and assess the enzymatic activity based on SCM3 acetylation. Depending on the strength of the effect we will define further experiments looking into cohesin functions.
This is a BEP project and will be carried out in the lab of Kerstin Wendt at the Department of Developmental biology /Erasmus MC. Results will be discussed with the clinicians at the Department of Clinical Genetics.

Further reading (click to link to article)

https://pubmed.ncbi.nlm.nih.gov/22885700/

(Example) projects submitted by lab in past years

(2024-2025) Migration of developing neuronal cells in brain organoids

This project is a collaboration with the group of Debbie van den Berg and will be performed under supervision Kerstin Wendt at the Erasmus MC and the Optical Imaging Center of the Erasmus MC.

We want to understand how neuronal development differs between healthy cells and cells haploinsufficient for NIPBL, an important regulator of the cohesin complex that is frequently mutated in a human developmental syndrome.
For this we have established brain organoids that contain both cell types. A very small fraction of both cell types is either labelled with mcherry of efgp, allowing us to image the migration of these cells in the organoid.
For this project we look for a student to establish tracking of those cells to identify differences in the behavior. The challenge is to identify the cells, track them over time and describe the tracks. Depending on the background and preferences of the student, this project can be a BEP or a MEP project. A MEP project would also include working with the cell cultures and imaging.

Techniques

  • Image analysis
  • Eventually organid culture and imaging

 

(2024-2025) Interactions of the cohesin regulator NIPBL with chromatin regulators

This project is a collaboration between the labs of Kerstin Wendt (supervisor) and the Erasmus MC and the Optical Imaging Center of the Erasmus MC.

We have identified several chromatin regulators that interact with the cohesin-regulator NIPBL. Several highly interesting regulators are very difficult to address with biochemistry methods. Therefore, we want to study their interaction with NIPBL using immunostaining of cells and correlation of the signals, eg. test whether the proteins colocalize throughout the entire cells cycle or not. Further, we will interfere with functions of NIPBL and test whether this changes the colocalization pattern.

Techniques

  • The project is a combination of cell culture, imaging and image analysis

 

Loop extrusion by cohesin in live cells

Supervisor: Kerstin Wendt, k.wendt@erasmusmc.nl

Contact us if you are curious.

Further reading

DOI: 10.1016/j.molcel.2023.07.024