Kinghorn Cancer Center
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]
Big congratulations to our PhD student Sam Rogers, who took out best poster at last weeks inaugural EMBL Australian PhD Symposium, held at UNSW. An amazing achievement considering that he is still only in his first year.
Well done Sam !
Here is a recent talk I gave to some members of the public at the Garvan Institute of Medical Research.
It is a very general and simple over-view of explaining 1) how cells in your body proliferate, 2) how this goes wrong in cancer, 3) the challenges we are facing in treating and killing cancer, and 4) most importantly how we hoping to improve current treatments in the near future.
A big thanks to all the fantastic Garvan Foundation Team who hosted, filmed, and edited the event.