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Our research in Australia: cholesterol, immune cells and collaborations

Today is the day we celebrate all things Australia. So as I write this, I'm wrapped up warm in my house in Scotland with my heating on full blast, reflecting on great memories of my recent family trip to Brisbane in Queensland.  There I was lucky enough to catch up with two of the scientists we currently fund at the amazing  Translational Research Institute (TRI) in Brisbane and find out how their collaborations  across different disciplines enhance their cancer research. Worldwide Cancer Research is currently funding eleven projects across Australia.

Here's what I learned from my trip down under.

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The Translational Research Institute (TRI) in Queensland

Research that goes from bench to bedside in Brisbane

In Brisbane, I discovered a city which is a real mix of the old and the new; traditional architecture right next to towering metal and glass skyscrapers. This mix is reflected in the kind of biomedical research that happens in the city.  Solid foundations at the ‘bench’ where scientists study disease at the molecular and cellular level, combined with the clinical research when treatments reach the patients' bedside.

This ‘bench to bedside’ approach in Australia has been stimulated by the building of the TRI in 2012.  It is the largest medical research institute in the entire southern hemisphere. There, scientists aim to turn basic research discoveries into practical applications for the patient.  Teams of researchers and clinicians from four different research institutions are brought together in the TRI building to encourage cross-collaboration. It's an incredible building too, boasting full-length glass walls and a greenery-filled outdoor room, designed to encourage transparency and teamwork amongst all at the institute.

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Dr Michelle Hill in her lab

Fats and cancer collide

It was there in the blazing sunshine in the TRI atrium that I met Dr Michelle Hill, a University of Queensland researcher. With our funding, Dr Hill investigated the role of high cholesterol in the progression of prostate cancer.

“Cholesterol is an essential component of the membranes that surround our cells and encloses key organelles within our cells” explained Dr Hill.  “Our results suggest that high cholesterol alters the composition and function of cellular membranes, leading to prostate cancer spreading.”

Dr Hill was also able to identify some of the background cell mechanisms behind this effect.

“We found two key proteins which enable the high cholesterol to prompt cancer spreading,” said Dr Hill. “Cholesterol acts like a magnet, pulling these two proteins to the surface of the cancer cell. This disrupts the function of the cell, makes it more aggressive and spreads it elsewhere in the body.”

Cholesterol in cells

Now follow up work by Dr Hill and her team suggests that changing membrane cholesterol alters the cellular architecture (cytoskeleton) in prostate cancer as well as melanoma, breast, ovarian and kidney cancers.  These recent findings confirm that targeting cholesterol’s role in cellular membranes could provide potential new treatment strategies for many types of cancer, not just prostate cancer.

“This research reinforces the importance of cancer patients maintaining low cholesterol levels, in consultation with their clinicians." Dr Hill told me.

Laboratory researchers and clinicians collaborating

Dr Hill has since been brainstorming with clinical colleagues from diverse disciplines including exercise physiologists and cancer nurses to determine if exercise and diet can effectively reduce or maintain membrane cholesterol levels thereby limit cancer spreading.  She told me that these kinds of collaborations come easily when you have a hospital right next door to the lab, plus a stunning atrium in the middle to meet in and discuss ideas.

I then grabbed a quick lunch (salad – low cholesterol, of course) and walked up the four flights of stairs to meet our next researcher, Dr Frances Pearson.

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Dendritic cells stained in blue and green fighting tumour cells stained in red. (Image from Cancer Immunotherapies Group)

A cheaper and safer cancer vaccine

Dr Pearson is working in the Mater Research laboratory of Dr Kristen Radford, on the fourth floor of the TRI.  After a guided tour of the building, we sat on the top floor looking out over Brisbane and she spoke to me about their work.

“We are particularly interested in a type of cell called a 'dendritic' cell, a human immune cell which has been described as the conductor of the orchestra.  They are the cells that generate and direct the immune responses,” explained Dr Pearson.

Dendritic cells have been used as a ‘cancer vaccine’ to activate the anticancer immune responses in the body. But the dendritic cells have to be removed first from the patient’s blood and manipulated in the laboratory, which is difficult and expensive. Dr Pearson and colleagues are investigating how to trigger a specific subset of ‘cancer fighting’ dendritic cells inside the body – saving lots of time and money.

“We have developed a ‘humanised mouse’ – a mouse with a human immune system. We did this by taking human stem cells from umbilical cords - which we get through donations from the maternity hospital in South Brisbane. We then inject them into mice that have no immune system of their own and grow this human immune system inside the mouse.”

It is with this humanised mouse model that they are using to test and develop a special ‘signature’ to help an antibody vaccine identify and activate this new type of dendritic cell in the body.

I learned that the ‘bench to bedside’ approach of the TRI is a two-way approach.  Clinical samples such as these human stem cells are invaluable for basic science research and researchers such as Dr Pearson.  Then, ultimately, it will be novel research discoveries in the lab that lead to better cancer treatments such as these vaccines that could activate dendritic cells in the body and potentially drugs that target the reduction in the cytoskeleton-cholesterol membrane link that Dr Hill has observed in cancer cells.

Happy Australia Day to all our Australian researchers and supporters, keep up the good work and I hope to visit you all again sometime soon!

Dr Lynn Turner Head of Research at Worldwide Cancer Research, overseeing the scientific research funding strategy of the charity. She has a PhD in immunology from the University of Bath. She has over 8 years’ experience in awarding research grants to scientists and has worked in similar roles for Cancer Research UK and The Royal Society.

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