Project Description

Prof. Frederic Meunier

The University of Queensland

Quantitative analysis of single molecule tracking in live cells: from Brownian motion to function

Advanced microscopy analysis and modelling

Friday 6 July 2018

Professor Frederic Meunier obtained his Masters degree in Neurophysiology at the Paris XI University, France in 1992 and completed his PhD in Neurobiology at the CNRS in Gif-sur-Yvette, France in 1996. He was the recipient of a European Biotechnology Fellowship and went on to postgraduate work at the Department of Biochemistry at Imperial College (1997-1999) and at Cancer Research UK (2000-2002) in London, UK. After a short sabbatical at the LMB-MRC in Cambridge (UK), he became a group leader at the School of Biomedical Sciences at the University of Queensland (Australia) in 2003. He joined the Queensland Brain Institute of the University of Queensland in 2007 and obtained an NHMRC senior research fellowship in 2009 renewed in 2014 with promotion. He became Professor in 2014 at the Queensland Brain Institute and is currently part of the Centre for Ageing Dementia Research.

Super-resolution single molecule imaging techniques have provided tremendous help to decipher molecular and cellular mechanisms. Fluorescent probes tagged to proteins of interest have allowed tracking of single proteins in various membranous compartments such as the plasma membrane. Single molecule imaging has been instrumental in our current understanding of the nanoscale organisation of the plasma membrane which contain small nanoscale domains enriched with various proteins and lipids. Nanodomains cause reduced diffusion of certain molecules via protein-protein, protein-lipid interactions, and cytoskeletal structures. These nanodomains facilitate biological functions occurring on the plasma membrane such as exocytosis, endocytosis and signalling. In this seminar, I will introduce single molecule imaging techniques and the challenges facing the field when dealing with terabytes of data to analyse on a daily basis. I will also present some recent results suggesting that mobility states and nanocluster organisation are dynamically regulated and involved in protein functions [1, 2]. Finally, I will conclude on the development of new technologies allowing single molecule imaging of subdiffractional endocytic structures [3, 4] as well as GFP-tagged and endogenous proteins for the first time.

1. Bademosi, A.T. et al. (2017) In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters. Nat Commun 8, 13660.
2. Kasula, R. et al. (2016) The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and engagement with the SNARE complex during secretory vesicle priming. J Cell Biol 214 (7), 847-58.
3. Joensuu, M. et al. (2017) Visualizing endocytic recycling and trafficking in live neurons by subdiffractional tracking of internalized molecules. Nat Protoc 12 (12), 2590-2622.
4. Joensuu, M. et al. (2016) Subdiffractional tracking of internalized molecules reveals heterogeneous motion states of synaptic vesicles. J Cell Biol 215 (2), 277-292.