Archives for posts with tag: Melbourne

In the summer of 2012-13 my daughter Katherine and her friends got together to make a short film during their holidays while they waited for their University offers.

Nearly two years later here it is.

 

 

sadako and golden cranesadako and golden bigsadako and golden boat

Paper Thin is based on the true story of Sadako Sasaki, who tried to fold 1,000 paper cranes to beat her leukaemia. This is an amazing short film directed by Elizabeth Duong with beautiful original music by Daniel Hernandez and Elle Graham. Don’t just take my word for it. Don’t just watch it. Don’t just like it.

Share Paper Thin to help make leukaemia HISTORY.

 

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Telomeres. Apparently that’s the new buzz word in cosmetics . They come in different sizes – as we age they shorten. It’s been suggested that we could lengthen them to cancel the effects of ageing, or shorten them to cure cancer. But what are they?

They’re an integral part of our chromosomes. The 46 long strings of genes in each human cell are folded up to form chromosomes, which we can see down the microscope. The telomeres are at both ends of each chromosome. They protect the ends of the chromosomes, and stop the chromosomes from sticking to each other. Chromosomes joining together can be a cause of cancer – more about how that works when we look at the promised breakage-fusion-bridge clay model (in stop motion hopefully!).

The green spots are telomeres on the blue chromosomes from a leukaemia cell. Spot the two abnormal "ring" chromosomes - no ends, no telomeres.

The green spots mark the telomeres on the chromosomes from a leukaemia cell. Spot the two abnormal “ring” chromosomes – no ends, no telomeres (answer next time).

As we age our telomeres get shorter. Telomere shortening has also been associated with other factors such as extreme psychological stress and toxins, including chemotherapy. As well as cancer, short telomeres have been associated with diabetes, cardiovascular disease, osteoarthritis and other diseases. But it also seems that measures like reducing stress, improving diet and exercise may stop or even reverse this premature telomere shortening.

Here’s the paradox – short telomeres can help trigger cancer, but once established the cancer switches on a telomere-lengthening mechanism (usually an enzyme called telomerase) to survive.

And so different researchers are trying contrasting approaches to manipulating telomeres for improved health.

On the one hand, some researchers are looking at the possibility of using the telomere-activating enzyme telomerase to reverse the effects of ageing. Some cosmetics are already available that contain a chemical that’s been reported to activate telomerase. This same chemical is being tested for use as a treatment for some diseases associated with ageing and short telomeres.

On the other hand, because cancers need telomerase to be able to divide indefinitely, other researchers are looking into the possibility of destroying telomerase as a cancer treatment.

These potential treatments will need extensive testing to see if they work and make sure they don’t have unwanted side effects.

From the search for eternal youth to understanding and curing cancer, we haven’t heard the end of telomeres.

INTERESTED IN MORE DETAIL?

A single fertilised egg cell becomes a mature human by growing and dividing into two, many times over. Each time a chromosome makes a copy of itself the telomeres lose a little bit off their ends. The older we get the shorter our telomeres become, so there’s a limited number of times a cell can divide.

That is, unless an enzyme called telomerase is turned on. This enzyme lengthens the telomeres. If you think about it, although most cells in our bodies are programmed to divide a limited number of times, some cells have been dividing for millenia – germ cells – eggs and sperm. It’s cells like these that need telomerase.

Most cancer cells are also able to divide indefinitely by switching on telomerase.

Once the telomeres are dangerously short the chromosomes can start sticking together and becoming abnormal. This stage is called crisis.  The cells don’t function properly, and are a cancer risk, and they stop dividing or self-destruct. There are “tumour suppressors” that look after this self-destruction, but occasionally a cell will bypass this (for example by having a mutated tumour suppressor gene), survive and divide. If the cells divide, these abnormal chromosomes can become more abnormal and turn on cancer genes or lose tumour suppressor genes.

HOW MY RESEARCH FITS IN

This process has mostly been studied in lab animals or cells grown in the laboratory in artificial conditions. So we can extrapolate and suggest that chromosomes with short telomeres can join together and cause cancer. Unfortunately chemotherapy is associated with shortened telomeres, and is a risk factor for leukaemia. These therapy-related leukaemias are usually marked by very abnormal chromosomes.  In my own research I’ve identified some abnormal leukaemia chromosomes that have been made by chromosomes joining together at the telomeres. This was done by identifying which chromosomes are joined together, AND by looking at the molecular content of the chromosomes. End-to-end joining of the chromosomes is actually a lot more common than it’s thought, at least for the abnormal chromosomes I’ve looked at. The similarity between risk factors for very abnormal leukaemia chromosomes and shortened telomeres is interesting.

One thing I’d like to do is find out how common this joining together of the chromosome ends is, in other types of abnormal chromosomes in leukaemia (AML), and eventually look at other cancers. It would help understand how these cancers are caused and possibly identify ways to prevent this. Other information from this type of study could identify more genes with a role in cancer. This opens up new possibilities for developing treatments.

“Abnormal chromosomes made by the end-to-end joining of two chromosomes….” – that sounds like a segue into the breakage-fusion-bridge cycle. More on that later.

FURTHER READING

E. Blackburn and E. Epel 2012. Too toxic to ignore. Nature 490:169-171 (about stress, disease and telomere shortening). Note, Elizabeth Blackburn is Australia’s only female Nobel Prize winner (in science at least) – she shared the prize for Physiology or Medicine in 2009 for her discovery of telomeres.

C. Buseman 2012. Is telomerase a viable target in cancer? Mutation Research 730:90-97

E. Callaway 2010. Telomerase reverses ageing process. Dramatic rejuvenation of prematurely aged mice hints at potential therapy. Nature 28th November 2010 (published online).

B. de Jesus et al. 2013. Telomerase at the intersection of cancer and aging. Trends in Genetics (available online 19th July 2013)

C. Harley et al 2011. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Research 14:45-56.

R. MacKinnon and L. Campbell 2011. The role of dicentric chromosome formation and secondary centromere deletion in the evolution of myeloid malignancy. Genetics Research International Article ID 643628

R. MacKinnon et al 2011. Unbalanced translocation of 20q in AML and MDS often involves interstitial rather than terminal deletion of 20q. Cancer Genetics 204:153-161.

T. Morin. http://www.dayspamagazine.com/article/spa-products-tale-telomeres A balanced article on telomeres in Dayspa Magazine online.

http://www.pozible.com/project/20784

Paper Thin.

It’s getting harder to find research funding these days – it’s also a big time sink. I’m exploring different ways to raise awareness of this leukaemia research project and funds to keep it going.

Shouldn’t the government fund research? The Australian government is the largest funder of Australian medical research through the NHMRC. But there’s not enough money to fund all the worthwhile projects. Researchers spent over 500 working years making applications to just one of the NHMRC’s funding schemes last year, at a cost of $66 million (British Medical Journal report). Only one in five of the applications was funded – that’s 400 years spent writing unsuccessful grant applications, 400 years of research that was foregone to write those grants.

This project is rare in that it is addressing a very severe type of leukaemia from a different angle to the projects that are attracting large amounts of grant funding.

Have a look at the About page for more information on the project.

One consequence of funding cutbacks is that once a project is halted, the researchers move on to something else and the momentum is lost – the project is not likely to get up again and the knowledge and expertise are lost. This project is very specialised, and is supported with very little manpower (just me really) in a diagnostic laboratory.

Elizabeth Duong is a young amateur film maker based in Melbourne. With the help of some very talented friends, actors and dancers, she’s making a film to support this research project. There’s an original film score by Daniel Hernandez, to be recorded by Essendon Symphony Orchestra. They are all donating their time. The film will help raise awareness of leukaemia and leukaemia research.

With the help of our very generous donors we have raised the modest funds that we need to make the film. Thank-you to all including Caroline, Sarah, Nicholas, John and our anonymous donors.

I’ll post more information on the film as it progresses but there are good details and some photos of the first filming session through the Pozible link. Also some examples of Elizabeth’s previous work. Have a look.

This is going to be a blog about research and cancer, but I wanted to set the scene with a little insight into my workplace. Cancer can make people think about questions of life and spirituality.

Today I was talking with two people who both lost their spouses to cancer a few years ago. Both had been treated at St Vincent’s Hospital, where I work. These people commented that it’s a special hospital. The staff really care, and there’s a spiritual dimension which really made a difference.

The hospital was founded by the Sisters of Charity to serve the poor of Melbourne. It still looks out for the poor and disadvantaged, including patients of modest means. It makes an effort to reach out to the homeless, the outcasts and the mentally ill. It also provides excellent care, being a teaching hospital and part of the University of Melbourne and the Australian Catholic University, and excelling in many areas of clinical research.

One thing I like about working at St Vincent’s is “Five Minutes on Friday” a weekly inspirational message from the Director of Mission. I thought I should share part of this week’s timely offering from Lisa McDonald.

“One of the curious quirks of having a job with the word ‘Mission’ in the title is that it is not unusual for people to expect you would have such things as:

1. A reasonable knowledge of Catholic heritage

2. The capacity to quote a scripture or two… or three

3. The phone number of the Sister’s convent on speed dial

and, here’s a curious one… a favourite Church season!

Highly convenient of me to have mentioned it because (aside from Christmas obviously), we’re about to start mine. Pentecost…. “

Which is a weekly reminder that the people we are trying to help, whether they have a faith or not, are more than just flesh and blood.