Marcel Mettlen, Ph.D. Email & Phone Number

Dallas, Tx, Us

Dallas, Texas, United States

The Live Cell Imaging Facility (LCIF) offers internal, external and commercial users access to a variety of state-of-the-art optical microscopes. Imaging modalities include laser-scanning and spinning-disk confocal, multiphoton, wide-field deconvolution, TIRF, single-molecule imaging and more. In addition LCIF offers help with sample preparation, data analysis, automation of data analysis and microscope maintenance.

Dallas

Dallas

- Consultant for questions regarding microscopy, cell biology, membrane traffic, endocytic pathways and intracellular sorting.- Coordination of multidisciplinary research teams and collaborations.- Training of new postdoctoral fellows, students and technicians in cell biology, live-cell imaging and quantitative image-analysis- Design, overlook and perform experiments.

My area of expertise is cell biology, molecular biology, biochemistry, high resolution 4D microscopy and computer-based image analysis. The methodical goal overarching my work is to study cell function by minimally-invasive experiments. To implement this approach, I am engaged in developing quantitative and multi-dimensional live cell imaging in combination with statistical models that allow us to identify in situ the spatial and temporal relationships between cellular outputs and underlying molecular activities. My current research is based on, and continues my work as Sr. research associate (see relevant section below).In addition, as staff scientist, I'm responsible to coordinate efforts of 2 research teams involved in an interdisciplinary project: (i) members of the Danuser lab at the Harvard medical school, responsible for the development of analytical software and (ii) members of the Schmid lab at the Scripps Research Institute, responsible for all cell-biological aspects. My responsibilities include (i) organization of regular meetings between the two coast-to-coast teams, (ii) coordination and standardization of experimental procedures, (iii) data management, (iv) supervision of microscopes, (v) provision of biological data for control analysis, (vi) critical analysis of software outputs, (vii) interpretation of valid computational data in a biological context, and (viii) proofreading of manuscripts, presentations, etc.

Fellow of the American Heart AssociationClathrin-mediated endocytosis (CME) is the major endocytic pathway in eukaryotic cells and defects in CME lead to human disease, including cancer and cardiovascular problems. It occurs via clathrin coated pits (CCPs) that are assembled from cytosolic coat proteins. While the function of core components in CME is increasingly well understood, the exact role of most endocytic accessory proteins remains unknown.Live cell imaging has revealed striking heterogeneity in the dynamic behavior of CCPs. We have developed methods that allow us to extract new mechanistic insight from this dynamic heterogeneity, shedding light on early stages of CME. Our experimental approach, i.e. the use of new and highly sophisticated tracking software, has been validated in Nature Methods (Jaqaman et al., 2008).This software has enabled us to identify three kinetically distinct CCP subpopulations; Furthermore, additional data strongly suggest that CCP maturation is gated by an “endocytic checkpoint”, which is sensitive to CCP loading and regulated by the GTPase dynamin. (Loerke, Mettlen et al., 2009).We have next addressed the role of endocytic accessory factors in providing input into the endocytic checkpoint. We have been able to propose a temporal hierarchy of 12 protein functions during early steps of CME. These data support the idea that accessory proteins can monitor coat assembly, membrane curvature and cargo selection, thereby providing input into an endocytic checkpoint that determines the suitability of CCP intermediates for progression and completion of their maturation process (Mettlen, Stöber et al., 2009).Finally, we have combined microscopical and biochemical assays to study the effects of cargo and adaptors on CCP maturation and the regulation of CME. Our results underscore the highly dynamic, and cargo-responsive nature of clathrin coats and illustrate the complexity of CCP maturation (Mettlen et al. 2010)

Since (i) most cancers are of epithelial origin, (ii) the tyrosine kinse "Src" is a key regulator of the actin cytoskeleton and (iii) apical endocytosis depends on actin, my main research was focused on how Src-activated signalling cascades affect cell polarity, apical membrane traffic and the apical endocytic machinery of polarized epithelial cells. It remained to be established whether basic mechanisms, deciphered in molecular terms in non-polarized cells, strictly apply to polarized endocytosis. My doctoral dissertation addressed these questions using epithelial cells harboring a thermo-sensitive mutant of Src. I established (i) the organization of the endocytic apparatus in early malignant polarized epithelial cells, and (ii) that the Rab5 effector, rabankyrin-5 defines a distinct Rab5 signaling pathway involved in Src-induced macropinocytosis. Interestingly, this system also shows striking similarities with, and could shed light on the triggered apical entry of enteroinvasive pathogens, and on the apical differentiation of osteoclasts. These results have been published in "Traffic (2006), 7: 589-603".In addition to this main research project, I contributed significantly in numerous collaborations, thereby expanding my publication record. Finally, my research has been combined with a teaching assistant position in cell biology at the Louvain University. These teaching duties required a 50% commitment of my time.

As teaching assistant at the Louvain University, Faculty of medicine, I autonomously supervised training sessions of image recognition exercises in cell biology, followed by ~250 students per year. Furthermore, I created and supervised a one-week practical course on cell biology for students in biochemical sciences.

Master, Cell Biology

Bachelor, Human- And Cell Biology