Grimm group

Lysosomal dysfunction can result in lysosomal storage disorders (LSDs) such as mucolipidoses but it is also implicated in the development of more common neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, metabolic diseases, retinal diseases and pigmentation disorders, trace metal deficiencies such as iron deficiency, and also cancer and immune diseases. Highly critical for the proper function of lysosomes, endosomes, and lysosome-related organelles (LROs) is the tight regulation of various fusion and fission processes and the regulation of proton and other cation concentrations within the endolysosomal system (ES). TRPML cation channels (TRPML1, 2 and 3) and Two-pore channels (TPC1, TPC2) have recently emerged as important regulators of such processes within the ES and appear to be essential for a proper communication between the various endolysosomal vesicles. We use endolysosomal patch-clamp techniques, molecular and cell biology techniques as well as knockout mouse models to study the physiological roles and activation mechanisms of these ion channels in more detail with the ultimate aim to explore the potential of these ion channels as drug targets for a range of different diseases.

iPSC culture
Induced pluripotent stem cells (iPSCs) are a type of stem cell that can be generated by reprogramming adult cells, such as skin cells, back into a pluripotent state.
iPSCs have the remarkable ability to differentiate into various cell types found in the body, including neurons, heart cells, and liver cells. Studying the effects of LSD mutations can be achieved by differentiating neurons into cortical and dopaminergic types. These neurons are then subjected to treatment with various compounds in order to identify potential future therapies for associated diseases

Endolysosomal Patch-Clamp
Endolysosomal patch-clamp is a technique used for electrophysiological characterization of ion channels present in endolysosomal membranes. It involves creating a patch-clamp configuration on the membrane of enlarged endolysosomal vesicles. By applying voltage and recording the resulting electrical activity, detailed insights into the function and regulation of endolysosomal ion channels can be gained, which play important roles in cellular processes and disease mechanisms.

Ca2+ Imaging
In the research of TRPML and TPC channels, Ca2+-imaging is used to investigate the activity of calcium ions in cells. By using fluorescent dyes that bind to Ca2+, real-time changes in Ca2+ levels can be visualized. Analyzing Ca2+ fluctuations provides insights into the function and regulation of these channels, which can contribute to the development of potential treatments for associated diseases.

Confocal Imaging
Confocal imaging is a technique used to capture high-resolution images of samples, such as cells or tissues, with improved clarity and contrast. It works by using a pinhole to eliminate out-of-focus light, resulting in sharper images with better optical sectioning. By scanning the sample point by point, confocal imaging enables three-dimensional reconstruction and visualization of the specimen.