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Cell Biology

The Cell Biology group is investigating new approaches for quantitative, high resolution, tracking and manipulation of proteins during the establishment of cell polarity (in both T cells and epithelial cells). Possible molecular links between the regulation of cell polarity, cell tension and cell division are explored through the utilization of both microfabricated cell supports and laser tweezing to manipulate tension in cells.


Project Overview:

Group:
Objectives:
This project is to develop and apply state-of-the art microscopic methods to assess the mechanisms and consequences of polarity and asymmetric cell division in lymphocytes.
Members:
Collaborators:
Prof. Steve Reiner
University Pennsylvania, USA
Dr. Helena Richardson
Peter MacCallum Cancer Centre, Australia
Prof. Ellen Robey
University of California Berkeley, USA
Dr. Patrick Humbert
Peter MacCallum Cancer Centre, Australia
Ms. Sarah Ellis
Peter MacCallum Cancer Centre, Australia

Research Overview:

The Cell Biology Laboratory was established in July 2005 to allow the wealth of novel technologies developed by the Centre for Micro-Photonics to be utilized in cutting edge biological experiments. An important attribute of this collaboration is the strong links between the Cell Biology Laboratory at Swinburne and the Immune Signaling Laboratory at the Peter MacCallum Cancer Centre (both run by Sarah Russell), which enable a fluid exchange between top quality photonics and biological research. We have established molecular biology and tissue culture facilities at the PeterMac, and begun a number of exciting projects involving collaborations between researchers at the PeterMac and many staff at the CMP. Many CMP technologies, such as microfabrication and laser tweezing, will be utilized in this work.

A number of projects have been initiated that will elucidate the mechanisms of action and physiological functions of a network of proteins that regulate cell shape, the "polarity network". The polarity network includes two proteins called Discs large (Dlg) and Scribble, which are also tumour suppressors in certain circumstances. Understanding how these proteins work will lead to important diagnostic and therapeutic opportunities in a number of diseases. Examples of two such projects are described below.
  • We are developing new approaches for quantitative, high resolution, tracking and manipulation of proteins during the establishment of cell polarity (in both T cells and epithelial cells). This project involves genetically engineering proteins to tag them with fluorescent markers, expressing them in cells, and imaging their movements while the cells undergo polarity changes. We will combine improvements in both sensitivity and computational analysis with genetic manipulation of the individual components of the polarity network, to elucidate the hierarchy of molecular events required for cell polarization.

  • It is becoming evident that for a number of cancers, disease progression is dramatically influenced by the surrounding normal tissue, and the polarity network plays an important role in communications between the cancer and its surrounding tissue. It has recently come to light that tissue rigidity and cell tension have important influences on cancer progression. We have initiated a program of research to investigate possible molecular links between the regulation of cell polarity, cell tension and cell division. This project involves the utilization of both microfabricated cell supports and laser tweezing to manipulate tension in cells, imaging of polarity proteins as in project 1, and correlation with activities associated with cancer, such as cell proliferation and death.


Figure left: Reorganization of polarity proteins during killing by a T lymphocyte.
Figure right: T cell undergoing asymmetric cell division.


Achievements for 2009
  • We have developed a super-resolution microscope capable of high spatial resolution imaging based on photoactivatable fluorescent proteins and/or photoswitchable emitters together with localisation algorithms. Our achievements include image processing software to identify and localise single fluorescent particles with high precision, and scripting functions to determine the photoluminescence trajectories of hundreds of single particles simultaneously. Preliminary results show protein localisation of conjugated quantum dots in cells.
  • We have written software for the measurement of protein diffusion using Raster Image Correlation Spectroscopy, and applied it to living cells. This work was the subject of a Masterís thesis by Raz Shimoni.
  • We convened our second Human Frontiers Workshop on Thymocyte Polarity, this time in Berkeley, California. Six members of the Swinburne and Peter MacCallum labs met with the Robey lab to discuss our progress in the Human Frontiers-funded project.
Aims for 2010
  • Further development of super-resolution technology, including imaging of photoactivatable proteins in T cells.
  • Continue development of software for tracking and analysing polarity in lymphocytes.
  • Continue elucidating the role of polarity and ACD in lymphocyte polarity and cancer..

Project Leader:
Professor
Sarah Russell

ph: +61 3 9656 3727
srussell@swin.edu.au

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