MY RESEARCH

One thread running through my scientific career has been the study of how cells respond to various forms of stress. During my PhD this mainly meant ER stress, which is an umbrella term roughly meaning that the Endoplasmic Reticulum (ER) can no longer function in a physiological way (ie. can no longer fold new proteins).

After my PhD I switched gears to work on autophagy, an important pathway cells use to deal with nutrient deprivation or damaged organelles, among others. Autophagy can be considered a waste disposal mechanism for cells, and as such plays a big role in keeping cells healthy.

 

As I transitioned between these research areas, another consistent theme emerged: investigating how proteins and protein complexes influence their surroundings. This was particularly intriguing in the context of lipid trafficking and membrane remodeling.

A key question when investigating a protein of interest is understanding how it carries out its function, either independently or within a complex. A method frequently utilized for this involves examining the interactome of target proteins, such as PERK and ATG9A, to shed light on observed cellular changes. Our investigation of PERK revealed a novel association with the actin cytoskeleton, which played a role in changing ER membrane contact sites. Meanwhile, our study of ATG9A uncovered previously unknown connections with lipid transport proteins. Links to these papers can be found under Pulications.

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The approaches I employ to address these challenges are varied, with microscopy playing a central role. In my work, the term "microscopy" encompasses a range of techniques, from light microscopy (spanning confocal to super-resolution methods like STORM) to electron microscopy (including Transmission Electron Microscopy and electron tomography). Furthermore, I also integrate these approaches through correlative light and electron microscopy (CLEM). Illustrative examples can be found in the images showcased on this website.
Besides these techniques biochemistry remains a workhorse in many cell biology projects, ranging from Western Blotting to in vitro assays. Especially when working with protein complexes, in vitro reconstitution and crosslinking techniques can be valuable. We have also used Hydrogen-Deuterium Exchange Mass Spectrometry to map details of protein-protein interactions, and negative stain and Cryo-EM approaches to gain structural insights into protein complexes.