Cancer

Latest News and Views Article now Online “Degrading Claspin away with Cdh1 and Cyclin A”.

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Great news, our latest article in @CellCycleJ is now online.

“Degrading Claspin away with Cdh1 and Cyclin A. Cell Cycle (2015)”

You can view the pre-print version here

The News and Views article is based on the recent publication by Oakes, V. et al. entitled “Cyclin A/Cdk2 regulates Cdh1 and claspin during late S/G2 phase of the cell cycle” Cell Cycle 13, 3302–3311 (2014).

Here is a sneak peak at the figure from our article.

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Public Talk “Killing Cancer One Cell at a Time ” now on YouTube

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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.

We will be at the Sydney Light Optical Users Meeting on July 24th 2014

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Great news, Cell Division Lab will be at the  Sydney Light Optical Users Meeting, hosted by Dr Pamela Young at Sydney University, this Thursday (24th of July).

I will be presenting a short seminar on “Imaging and Analysing Cell Division”.

If you would like to attend please contact Pamela asap. Her details are below!

Hope to see you there !

Sydney Light Optical Users Meeting July 2014

Anti-Oxaidants and Cancer…A complicated story!

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There has been a bit of press lately suggesting that Antioxidants might actually be bad for cancer… not good as they are commonly promoted in the media.
IFLS has put together a great article on some of the reasons why antioxidants might not be such a great thing [Link].

In addition, we recently wrote a review article about how different ‘stresses’ including oxidation can affect mitosis, and cancer. We also came to a similar conclusion in our review,  that antioxidants were a complicated and not always benifical for treating cancer. One of the main reason we suggested this was due to the fact that many common antioxidants are part of the Flavonoid family. On the surface that sound great, but many Flavonoids also happen to potently inhibit cyclin dependent kinases (Cdks). Coincidentally, our other recent article in Cell Cycle, showed that partial inhibition of Cdk1 can dramatically disrupt mitosis and drive severe cytokinesis defects and polyploidy (see video below). These mitotic defects are the foundation of chromosome instability  (CIN), which is a hallmark of more aggressive cancer types, that are also resistant to most chemotherapies and treatments. In simple terms, there is a possibility that in some cases, taking large quantities of dietary Flavonoids (e.g red wine, dark chocolate etc) could drive the formation of more aggressive cancers. This is definitely an area that needs a lot more research, and as always make sure that you fully discuss any dietary and supplements with your oncologist.

 

This is what happens when a ‘fairly normal’ cancer cell is treated with low doses of a Cdk1 inhibitor.

Here is a picture of a polyploid cancer cell, which was produced by partially inhibiting Cdk1.

ImageJ=1.48f unit=micron

 

Our Latest Review Article “Stressing Mitosis to Death” is now online !

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Great news, our latest review article “Stressing Mitosis to Death” has been accepted for publication by Frontiers in Oncology. You can access the provisional pre-press version here.

The review is about how common stresses affect mitosis, and the impact these stresses can have on the blockbuster mitotic chemotherapy drug Taxol (paclitaxel)

Finally here is one of the beautiful figures drawn by our own Sam Rogers for the Review!  Hope you enjoy the read !

 

Fig. v4

A brief Intro to Greatwall Kinase…The King of Mitosis

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Our favourite protein in the lab is Greatwall kinase. It was first discovered in 2004 to be critical for cell division in fruit flies (1,2) . The trail then went cold for a few years as to its exact function, but in 2009, while I was working as a post-doc in France, I was fortunate enough to be in the lab that uncovered its exciting mode of action. For cells to get into mitosis they must activate a key protein called cyclin dependent kinase 1 (Cdk1). I like to think of this as the accelerator in a car. So to get moving cells push on the gas!
And conversely to get out of mitosis you need to hit the brakes. These brakes are the phosphatases which reverse the action of kinases like Cdk1. That’s great but what is missing from this equation?
Well like any car it’s pretty useless without a driver to co-ordinate the accelerator and brakes. And this is where Greatwall (Gwl for short) comes in. It makes sure that when Cdk1 (accelerator) turns on that the breaks get turned off and vice versa (3,4). Without Gwl the cell gets into a lot of trouble very fast, which you can see in the image below. Here I depleted the human version of Gwl (a gene called MASTL) and watched what happened as cells tried to undergo mitosis (5). As you can see they don’t do a very good job… the result is cells fail to divide correctly, resulting in multiple defects and often cell death.

Gwl Figure

I hope you enjoyed part one of my feature on Gwl, and in part 2 I will into more details about this amazing and exciting new protein.

References:

1. Bettencourt-Dias, M. et al. Genome-wide survey of protein kinases required for cell cycle progression. Nature 432, 980–987 (2004).

2. Yu, J. et al. Greatwall kinase: a nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila. J Cell Biol 164, 487–492 (2004). [Link]

3. Vigneron, S. et al. Greatwall maintains mitosis through regulation of PP2A. EMBO J 28, 2786–2793 (2009). [Link]

4. Lorca, T. et al. Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle. J Cell Sci 123, 2281–2291 (2010). [Link]

5. Burgess, A. et al. Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance. Proc Natl Acad Sci USA 107, 12564–12569 (2010). [Link]

Our New Name is the “Cell Division Lab”

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After some deep thought and consultation with my lab, I have decided to change the lab name from the Mitotic Control lab to the more flexible and public friendly “Cell Division” lab. We feel this name is much simpler to understand, especially for those that are not specialist in the field. It also provides more flexibility for our future research goals, which may take us beyond the control mechanisms that govern mitosis.
All the best

Andrew Burgess
Head of the Cell Division Lab

Excellent Night at Young Garvan Forum.

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I was lucky enough to attend the 3rd Young Garvan Forum for 2013last night on “How close are we to finding the cure for cancer?”.

There were 4 great talks from including 2 from Dr Marina Pajic and Dr Paul Timpson who are fellow researchers here at the Garvan.

The standout talk was by Mr Ben Bravery, who is a young adult Colorectal Cancer Survivor. He has an excellent blog about his personal fight with cancer, which is an excellent read and resource for other cancer patients.