Arumugam Lab research
About Dr Senthil Arumugam
Dr Senthil Arumugam obtained his Masters of Science by research degree from Tata Institute of Fundamental Research in 2008 in Mumbai, India. There he worked on multiphoton imaging of neurotransmitters with Professor Sudipta Maiti. He received his PhD training in the lab of Professor Petra Schwille at the Max Planck Institute for Cell Biology and Genetics in Dresden, Germany in 2012, focusing on self-organisation and self-assembly of proteins involved in bacterial cell division.
From there, Dr Arumugam joined the labs of Professor Patricia Bassereau and Professor Ludger Johannes at the Curie Institute, Paris, France, as a joint post-doc between the physical chemistry and biology departments, where he worked on protein-membrane interactions and cellular trafficking. Dr Arumugam joined Single Molecule Science at the University of New South Wales as an independent group leader in September 2016 and established the Lattice Light-Sheet (LLS) Imaging infrastructure with his research focused on endosomal trafficking.
In October 2019, Dr Arumugam joined EMBL Australia as a Group Leader at the Monash Biomedicine Discovery Institute, with the lab focussing on fundamental questions in intracellular trafficking and their role in cell fate specification and pattern formation in development using LLSM and MOSAIC. At the Monash BDI, Dr Arumugam aims to build the next generation Lattice Light-Sheet Microscope with adaptive optics, enabling observation of sub-cellular details in vivo, tissues and organoids enabling physiologically relevant studies and observation of emergent properties that otherwise may not be observable in cell cultures.
We aim to understand how complex properties arise out of molecules and their interactions, with a primary focus on endosomal trafficking at the level of single cells and in the context of intercellular communications in development. To enable this, we use advanced fluorescence imaging and spectroscopy methods that include Lattice Light Sheets, Adaptive Optics based light sheets, single molecule imaging and other related techniques, complemented by computational data analysis and mathematical modelling.
Our broad areas of interests are:
Principles of subcellular organisation and transport
A living cell is an active dynamic system where all the non-living constituents of a cell organise themselves through a complex set of interactions, integration of physical principles that gives rise to a ‘living’ cell. Within a living single cell, there are millions of interactions going on between tens of thousands of components. One central component of cellular life is vesicular traffic on the cytoskeleton network inside the cells. Quite analogous to how a city is organised with general public transport systems consisting of buses, light rails, and trains, specific highways for long distance transport, cars, motor bikes etc. the inside of the cells have self-assembled, polymerized proteins building up the tracks, membrane vesicles (endosomes) that carry specific cargoes building up the transport carriers, and the motor proteins that generate the force to pull the membrane vesicles to move along the tracks building up the transport system. However, unlike a train or a bus, the transport inside cells is quite stochastic, i.e. the endosomes can randomly stop, change directions or run for a random length.
The fundamental questions that we ask in our lab are:
- Like the transport map of a city, what are the molecular codes governing trafficking of cargoes inside cells?
- What regulatory networks/ mechanisms operate to reduce or overcome the intrinsic stochastic nature of the system, and
- How does intracellular trafficking of receptors govern temporal dynamics in signalling within a cell and in a group of cells?
Overview of endosomal transport in a single cell
Stochastic processes building up endosomal trafficking
of EGF receptor within very early endosomal populations in a live cell imaged using LLSM.
distinct endosomal markers Imaged using LLSM at 4 seconds per volume.
to golgi and plasma membrane.
The plasma-membrane of the cell are highly heterogeneous in their lateral organisation and their interactions with embedded and peripheral proteins. This heterogeneity is an important parameter in providing mechanisms by which various biological processes are regulated. The cell-membrane is highly complex and dynamic and required capturing processes in real time to be able to understand them. In the past, using giant unilamellar vesicles formed from a quaternary lipid mixture, we have demonstrated experimentally the effect of a cytoskeletal pinning on phase separation and coexistence in freestanding multicomponent lipid membranes. We also investigated the hypothesis that the thermal fluctuations of the membrane could drive membrane associated proteins or nanoparticles to cluster together, in a similar manner to Casimir forces.
Currently, we are interested in membrane protrusions on living cells. Cells, for a plethora of processes utilize thin, flat, branched actin cytoskeleton filled membrane protrusions like lamellipodia and membrane ruffles. While actin filaments are helical, with the probability of branching in all directions, most cellular protrusions are 2-dimensional. This project aims to understand how dynamic flat protrusions are initiated and sustained when arising out of an essentially flat membrane using a combination of advanced fluorescence microscopy, in vitro reconstitution technique and simulations and modelling.
optogenetic excitation of PA Rac1 on the Lattice Light Sheet Microscope (LLSM).
Actin cortex – membrane interactions
Endocytosis and endosomal regulation by alternative splicing
Tissue specific alternative splicing (AS) is important for tissue maintenance and proper functioning of the respective cells. While AS at the level of sequences of isoforms are known, what dynamic structural alteration do they render, and what are the functional consequences of AS, physiological roles of splicing events within the context of a specific tissue remain unknown. Here, using, cutting edge high-resolution and fast imaging complemented with computational analysis, we aim to understand how splicing functions to regulate endocytosis and endosomal trafficking machineries.
Tracking endosomes and associated cargo
Our general principle is to observe processes in action, measure parameters quantitatively and complement approaches like mathematical modelling, molecular simulations etc. We strive to employ the most appropriate technique that allows us the best possible quantitative measurements for a given sample/ experimental system. Fast volumetric imaging techniques are appropriate to measure stochastic processes like endosomal trafficking, conversions etc. The experiments allow measuring and tracking every endosome at whole cell level, facilitating unprecedented parametrization of the processes. We envision our studies to lead to precise mathematical modelling of these processes. We use Lattice Light Sheet Microscopy to image endosomal trafficking and membrane protrusions in live cells, complemented with single molecule imaging, super resolution (DNA-PAINT, STORM, PALM, SIM). We also implement other fluorescence techniques including optogenetics, FRET, FCS, FRAP as required.
We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Student research projects
The Arumugam Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.