Dr Senthil Arumugam - UNSW

Dr Senthil Arumugam - UNSW

Location: 
Davis Auditorium
Start Time: 
Tue, 18/06/2019 - 2:00pm
End Time: 
Tue, 18/06/2019 - 3:00pm

​Decoding the Dynamic Endosomal Matrix

​Special seminar hosted by Sandra Nicholson & Kelly Rogers

Multi-cellular life processes such as proliferation and differentiation depend on ligand sensing receptors at cell surfaces that can dynamically internalize to decode information at single cell levels. Following internalization, receptors are localized in endosomes that transport the receptors to their intracellular destinations to curate the downstream signaling events. In case of epidermal growth factor receptors of the receptor tyrosine kinase family, EGF activated receptors are robustly trafficked to the peri-nuclear region that is enriched in phosphatases. We asked if there exists an EGF receptor-specific modulation at the level of very early endosomes that govern the accumulation at the peri-nuclear region. Here, using lattice light-sheet microscopy (LLSM), we reveal an EGF- APPL1-dynein interaction cascade that mediates a cohort movement of EGFR bearing endosomes to the peri-nuclear region within the first ten minutes of endocytosis. We envision that such mechanisms may modulate the time of transit from the plasma membrane to the perinuclear region determines the duration of signaling by a subset of activated EGFRs enabling more resolved sensing of time-varying morphogen signals. We anticipate our approach using live cell-based study of conditional trafficking such as receptor stimulation be a starting point in revealing transient yet functional interactions such as the EGF stimulation-dependent engagement of APPL1 and dynein described here. I will also describe actin-related membrane topology studies using LLSM and general advances in virtual reality based quantification approaches.
 
Dr Senthil Arumugam obtained his PhD training in the lab of Prof Petra Schwille at the Max Planck Institute for Cell Biology and Genetics in Dresden, Germany. His post-doctoral work in the labs of Prof Patricia Bassereau and Prof Ludger Johannes at the Curie Institute, Paris, France focussed on protein-membrane interactions and cellular trafficking. He was also a visiting researcher in the labs of Prof Melike Lakadamyali, ICFO, Barcelona, Spain, Prof Tomas Kirchhausen, Harvard Medical School, USA, and Prof Satyajit Mayor, National Centre for Biological Sciences, Bangalore, India during which he worked on super-resolution techniques, Lattice light sheet-based imaging and homo-FRET imaging.  Dr Arumugam joined Single Molecule Science, UNSW as an independent group leader in September 2016. His lab currently focusses on utilizing cutting-edge fluorescence based technologies to address cell-biology problems with current emphasis on endosomal trafficking.