EPFL BioEngineering Talks

Weekly BioEngineering Talks (Lunch Provided)

INVITED SPEAKER:

Intracellular architecture and mechanics: new rheostats of metastasis
Dr. Jacky Goetz, INSERM / University of Strasbourg
Host: Prof. Li Tang

Abstract:
Emerging evidence suggests that the function and position of organelles, together with their mechanical adaptation of cells, are pivotal for tumor metastasis. Lysosomes integrate metabolic sensing with gene regulation and protease secretion, while circulating tumor cells (CTCs) must adjust their mechanics to overcome constraints during hematogenous spread. Yet, how spatial distribution of organelles and how cell-intrinsic mechanics control metastasis remains elusive. Here, we analyze lysosome subcellular distribution in patient-derived melanoma cells and biopsies and show that lysosome spreading scales with melanoma aggressiveness, while in parallel assessing how CTC deformability affects dissemination and identifying mechanical phenotypes that favor metastatic extravasation. Using chemo-genetic control of lysosome positioning, intravital microscopy with CTC-mimicking beads, mechanical tuning in tumor lines and profiling of patient-derived cells, we demonstrate that perinuclear lysosome clustering impairs secretion, matrix degradation and invasion, and that the mechanical properties of circulating objects dictate their ability to enter constraining vessels. We identify cellular viscosity as a rheostat of CTC circulation, arrest and extravasation, and show that impairing lysosome spreading significantly reduces invasive outgrowth in mouse and zebrafish models, with traits that favor extravasation and outgrowth being partially distinct. Altogether, these findings establish lysosome positioning and CTC viscosity as key rheostats of metastatic progression and suggest their potential utility for diagnosis and therapeutic targeting of metastatic cancers. Whether they are interconnected determinants and how they control immune surveillance will be our next goals

Bio:
Jacky graduated in Pharmacology and Cell Biology from University of Strasbourg (France) in the laboratory of K.TAKEDA. He then moved to the laboratory of I.R. NABI in Montreal (University of Montreal, Canada), and later in Vancouver (University of British Columbia, Canada), where he obtained his Ph.D. in 2007. He performed two postdoctoral stays, one at the CNIC in Madrid (Spain) in the laboratory of M.A. DEL POZO, and one in the lab of J.VERMOT at the IGBMC in Strasbourg (France). Fascinated by tumor metastasis, its mechanical aspects and the use of state-of-the-art microscopy approaches in several animal models, he created the TUMOR BIOMECHANICS LAB in 2013. Quickly joined by a team of experts in imaging, mechanobiology, extracellular vesicles, he built a task force aiming at further dissecting the mechanisms and mechanics of tumor dissemination. The team made several exciting discoveries around tumor metastasis that were acknowledged by several prizes (SBCF, Ruban Rose, French Academy of Sciences, Fondation de France, EuroLife). When he is not in the lab, Jacky is either running, swimming or biking and loves competing during half IronMan triathlons (70.3). You can also find him traveling with his family, during sabbaticals (Australia, South Africa), always thinking about the next trip. Fascinated by Japan but also by Alsace, where he grew up, he could « kill » for sushi and loves the alsatian architecture

STUDENT SPEAKER:

Structural Analysis of Intravenous Immunoglobulin (IVIG) Interactions with Enteroviral Surfaces Using Cryo-EM Based Polyclonal Epitope Mapping
Yash Garodia, Antanasijevic Lab


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BioEngineering Talks mandatory EDBB Seminar Attendance (1st-Year PhD Students)

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