8th Garvan Signalling Symposium
We welcome scientists at all levels, including students, post-docs, research staff and senior lab heads. The intimate nature of the meeting and enjoyable social functions promotes a collegial atmosphere and excellent networking opportunities. A poster session will be held on the Monday afternoon with generous prizes. Slots have been reserved for short (15 minutes) talks to be selected from submitted abstracts.
The meeting is held at the Garvan Institute in the glamorous Darlinghurst region of Sydney, close to the city, Oxford Street, King’s Cross and the harbour.
This years exciting program features state-of-the-art technologies to investigate a wide range of diseases including cancer, immunology, neuroscience and metabolic disorders. Special sessions focus on in vivo/intravital signalling, proteomics, control of gene regulation and the structural basis of signalling.
Click Here for more information and to register
A defining feature in over 2/3rds of all solid tumours is the continual loss and gain of whole are small parts of chromosomes. This instability, or CIN for short, strongly implicated in tumour initiation, progression, chemoresistance and poor prognosis. CIN is created through failures during mitosis, whereby whole or parts of a chromosome are segregated incorrectly, thereby created daughter cells with unequal chromosome numbers. Consequently, understanding how mitosis is regulated is essential for uncovering the mechanisms allowing CIN to arise and drive cancer. In our recent publication, we discovered the mechanisms controlling the key regulatory pathway critical to ensuring cells exit mitosis correctly. At the centre of this pathway is a gene call MASTL (short for ‘Microtubule Associated Serine/Threonine Kinase-Like’). The primary function of MASTL is to ensure that the cellular breaks (the phosphatase PP2A), is turned off during mitosis so that the accelerator (Cdk1 kinase) can drive the cell into mitosis. Much like a car, having the accelerator and breaks on at the same time is a bad idea, unless you like the smell of burning rubber. To successfully exit mitosis, and to perfectly segregate chromosomes, the cell must take the foot off the accelerator and turn on the breaks. Because MASTL is the central regulator ensuring the breaks are coordinated with the accelerator, it is essential to understand how MASTL is controlled. To this end, we uncovered that MASTL must be rapidly turned off to allow cells to exit mitosis, and this inactivation is carried out by another cellular brake call PP1 phosphatase (Rogers et al, JCS 2016). Now that we have identified and mapped this novel mitotic exit switch, we hope to be able to shed new light on how CIN drives the initiation and evolution cancer. We believe that with further study we will be able to better predict patient response to chemotherapy, and also identify new ways to ‘switch off’ highly unstable tumours, thereby improving treatment for patients that currently have a very poor prognosis.
Image of Interphase HeLa cell stained for Actin (red), DNA (blue) and the co-localisation of MASTL and PP1 by Proximity Ligation Assay (PLA; green).
Credit: Sam Rogers and Cell Division Lab
Great news, we have a new Mini-Review published in Frontiers Oncology entitled “Clinical Overview of MDM2/X-Targeted Therapies“, which is apart of the Research Topic Human tumor-derived p53 mutants: a growing family of oncoproteins
Here is a little snippet from the Abstract to wet your appetite!
MDM2 and MDMX are the primary negative regulators of p53, which under normal conditions maintain low intracellular levels of p53 by targeting it to the proteasome for rapid degradation and inhibiting its transcriptional activity. Both MDM2 and MDMX function as powerful oncogenes and are commonly over-expressed in some cancers, including sarcoma (~20%) and breast cancer (~15%).
In this overview, we will review the current MDM2- and MDMX-targeted therapies in development, focusing particularly on compounds that have entered into early phase clinical trials. We will highlight the challenges pertaining to predictive biomarkers for and toxicities associated with these compounds, as well as identify potential combinatorial strategies to enhance its anti-cancer efficacy.
The article is Open Access, which means its free for everyone and anyone to read and download!
You can view and download it directly here [Link]
Its no secrete that Funding for Science in Australia, and around the world (see refs below), is in decline. The result is lower and lower success rates. While we wait for the #NHMRC to release the outcomes for 2015, the word on the street is that we can expect only 10-12% of grants to be successful. In other words, for 90% of Australia’s researchers they are wasting ~3 months of the year for nothing. Consequently as the funding pool decreases, funds naturally flow towards ‘sure bet’ senior researchers. This means that this wasted time is felt the hardest by early- and mid- career researchers (#EMCRs) who cannot compete with the long CVs of their senior peers, and are seen as a potential risky investment. Below is a graph I put together from the 2013 data, which is the most up to date information currently at hand. This trend of funding more senior researchers is clearly seen in the massive increase in average age of the CIA (chief investigator) on project grants over the past 30 years. It used to peak around 40 years, which perfectly aligned with the drop off in fellowships. So there was a very clear and clean transition from Post-Doctoral Funding for those that wanted to transition to a team leader role. However now, the average age has shifted to >50 years. This has created a significant 10-15 year ‘Funding Hole’ for EMCRs, where there are very limited number of fellowships on offer, and little to no chance of securing a project grant. While there has been a lot of talk about this black box, no solution or action has been taken to stem the loss of young, bright and talented researchers being forced out of research. Without action soon, we run the real risk that there will be no succession plan, and Australia’s ability to remain internationally competitive will be set back decades.
Great News, we have a new review article that has just been published online today in Inside the Cell!
Its Open Access, so that means its free for everyone to read!
During mitotic exit, phosphatases reverse thousands of phosphorylation events in a specific temporal order to ensure that cell division occurs correctly. This review explores how the physicochemical properties of the phosphosite and surrounding amino acids affect interactions with phosphatase/s and help determine the dephosphorylation of individual phosphorylation sites during mitotic exit.
The Full Reference and link for the Article can be found below:
Samuel Rogers, Rachael McCloy, D Neil Watkins and Andrew Burgess Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit Inside the Cell [Link]
Great news we are currently looking for a new honours student for 2016.
The title of the project is “Developing novel biosensors to monitor DNA damage in cancer cells”.
Its a very exciting new project incorporating cutting edge microscopy and fluorescent biosensors.
If you think you have what it takes and are interested please feel free contact myself, or UNSW SoMS.
For more information on the UNSW honours program please visit: http://medicalsciences.med.unsw.edu.au/students/soms-honours/
Below is an example of the images that will be created during the project.