Microscopic behaviour of developing breast cells uncovered Posted on March 2, 2021March 10, 2021 by Carly du Toit An improved high-tech fluorescence microscopy technique is allowing researchers to film cells inside the breast as never seen before. This new protocol provides detailed instructions on how to capture hi-res movies of cell movement, division and cooperation, in hard-to-reach regions of breast tissue. The technology – called multiphoton microscopy – uses infrared lasers to illuminate fluorescently labelled breast cells without harming them, so that elusive cell behaviours can be observed within living tissue. With the new method, WEHI researchers have revealed how breast cells rearrange, interact and sense their environment as the breast grows during development and recedes after lactation. Cell imaging within living tissue has been achieved in many organs but the breast has remained especially challenging. So far, this new method has revealed exciting and unexpected details of breast biology and will help teams worldwide to advance research on breast development and cancer. At a glance An improved imaging protocol is allowing researchers to film cells as never seen before. This new application of high-tech microscopy has enabled the imaging of stem cells as they guide breast development, and immune cells as they monitor the breast ducts to keep them healthy. By imaging living, moving cells in their natural setting, researchers can better understand how our bodies function in real-time at the microscopic scale. Understanding cell function The protocol was developed by researcher Dr Caleb Dawson, in a team led by Professor Jane Visvader and Dr Anne Rios, in collaboration with Dr Scott Mueller from the Doherty Institute, and published in Nature Protocols today. Dr Dawson said the filming technique unlocked a variety of applications to better understand how cells function, interact and develop. “One of the most valuable things we have been able to film with the technique are the terminal end buds (TEBs) in breast tissue,” he said. “These are club-like structures at the tips of the mammary ducts that grow during puberty to produce the branched tree structure of breast tissue. The unique cells inside the TEBs have never been filmed like this before so it was fascinating to watch this process for the first time.” “We have watched a cell behaviour inside the TEB that was hypothesised in the 1980s but was never proven, and which has implications for breast stem cell function.” Previously, TEBs had been studied by dissociating the individual cells and filming them outside the breast or by taking still images. With these approaches it is difficult to know how the cells actually behave and interact in living tissue. “By filming the moving cells inside intact breast tissue in laboratory models, we are able to grasp a better understanding of how the cells behave and cooperate to help the breast to form and function properly.” Dr Dawson said that he was grateful for the brilliant team and the cutting-edge technology provided by the Center for Dynamic Imaging at WEHI that made this work possible. “When we embarked on our mission to film these processes, I had little knowledge of the effort it would require. With the vision of leading breast researchers Professor Visvader, Dr Rios and Professor Geoff Lindeman, alongside the live imaging expertise of Dr Mueller, and the microscopes available, we were able to achieve something that very few labs in the world have accomplished,” he said. Opening the doors to new research opportunities Dr Dawson said the filming technique could be applied to a host of research endeavours. “Our approach enables us to image up to six fluorescent colours at the same time, which allows us to see how more cell types interact,” he said. “We can image different stages of breast development, immune cells, lymph nodes and hair follicles and watch how individually-labelled cells function.” “This means we can create beautiful images with extremely fine details about the cell shapes to get a better understanding of how cells interact and change over time. This opens up many new research opportunities and we are only just starting to see the potential of what this could be used for.” Dr Dawson said he hoped the imaging protocol would make this type of imaging more widely accessible to researchers. “There are very few research institutions doing this really high-end imaging, so it is great that we have this capacity in Melbourne and can share it with research teams worldwide.” The original news article was posted on the WEHI website. Video courtesy of WEHI. ACRF has awarded $10m in grants to WEHI for cancer research. Our esteemed Medical Research Advisory Committee ensures that only the most promising cancer research initiatives in Australia receive our funding. If you would like to financially contribute, please go to acrf.com.au/donate
Beneath the surface of skin cancer patients Posted on September 16, 2015March 14, 2018 by Carly du Toit Here at the ACRF we are proud to equip Australia’s leading cancer researchers with the resources they need to end cancer. Recently, a team of researchers from the University of Queensland discovered a protein that helps to control an important process in cell adhesion that is disrupted when someone contracts a disease such as skin cancer. The researchers said that the Australian Cancer Research Foundation Cancer Biology Imaging Facility at UQ’s Institute for Molecular Bioscience (IMB) played a vital role in this research. It is currently one of the largest and most comprehensively equipped facilities in Australia for both the imaging and screening of chemical and biological libraries. The facility was founded in 2010 with a $2.5 million ACRF grant and is home to 23 high-performance microscopes and supporting image data analysis workstations. PhD student Rashmi Priya at IMB says that what the research has done is clarify the role of the protein myosin in tissue integrity. “The protein Myosin is found at cell connection points and we now know that it plays a crucial role in regulating how cells stick together to form tissues in the body,” she said. “Our research has shown that this is because myosin protects a switch that acts as a stabiliser. This switch must be very tightly controlled as it affects many processes within the body. Too much or too little of this switch, or having it in the wrong place, can lead to diseases such as skin cancer, says Priya.” Professor Alpha Yap, who led the research team, says “The cells in all the tissues of our body die and have to be replaced as regularly as every 24 hours in the intestinal system. For this to happen, adhesion between cells must be carefully broken down and rebuilt, and we now have a better understanding of what it is that’s controlling this whole process.” The original article was published on the Institute for Molecular Bioscience website, click here to read more.
International gene study identifies five new melanoma risk regions Posted on August 24, 2015March 14, 2018 by Carly du Toit An international study led by QIMR Berghofer cancer researcher, Dr Matthew Law, has uncovered five new gene regions which increase a person’s risk of melanoma. Melanoma is the third most commonly diagnosed cancer in Australia, and although there are effective treatment options available to those who detect it early, the five-year survival rate of patients with more advanced cases is only 10%. “Each day around 30 Australians are diagnosed with melanoma, and from that more than 12 hundred a year lose their battle with the disease,” says Dr Law. “So each little piece of knowledge that we uncover is crucial as it affects the overall picture and helps us to continue to develop and improve the ways we detect and treat it.” The study found five new regions of the genome associated with melanoma and formally confirmed two more that were suspected to be risk factors. This research takes the total number of known melanoma gene risk regions to 20. “Most of the major gene risk regions previously identified are associated with pigmentation, or the number of moles a person has. The five new gene regions we’ve discovered are from different pathways, so it’s yet another piece to add to the melanoma puzzle.” “Out of the new regions that were found, the most interesting biologically, was one involved with the maintenance, development and length of the telomeres. Telomeres are like shoelace caps at the end of each strand of DNA that protect our chromosomes from damage. We know that loss or damage to telomeres is a key factor in the development of cancer cells.” Over 12 thousand melanoma samples were used for the project, making it the largest genome wide association study (GWAS) to identify variations associated with melanoma. The international collaboration of researchers from QIMR and the Melanoma Genetics Consortium (GenoMEL) are now preparing for an even larger study which is expected to find more markers of risk. “Our long term goal is to find drugs that modify the pathways that we’re identifying – that way we’ll be able to alter specific activity and bring it back to normal.” “It’s very exciting to find something new about a serious condition – that’s the joy of doing this kind of research. Working in science is all about discovering new things that haven’t been seen or understood before and hopefully add a bit more knowledge to the world.” QIMR Berghofer Medical Research Institute has received $6.65 million in grants from the ACRF which has funded technology to progress research in colon, breast, ovarian, prostate, leukaemia, lymphoma and melanoma. The original article was published on the QIMR Berghofer Medical Research website.
Researchers expose how ‘James Bond’ cells are made to boost our immune system against cancer. Posted on June 23, 2015March 14, 2018 by Carly du Toit Our determination to understand how our bodies operate continues to reveal fascinating intricacies. New research published in the journal of Nature Immunology exemplifies this. In the study, researchers from the ACRF funded Walter and Eliza Hall Institute reveal how immune cell ‘spies’ are created. These dendritic cells, or ‘James Bond’ cells gather information on disease-causing agents to aid our bodies in fighting them. “Dendritic cells are the intelligence-gathering cells that educate the immune system,” said Dr Naik from the Walter and Eliza Hall Institute. “They tell the infection-fighting T cells and NK cells what a virus, bacterium, fungus or cancer looks like so they know what they’re looking for when fighting disease”. Prior to this discovery, it was thought that dendritic cells shared one ‘parent’. But researchers have found that we actually have an army of unique ‘parent’ cells that decide whether or not to multiply or generate new dendritic cells to help identify and fight disease. What this new knowledge provides us with are clues on how the immune system could be manipulated to better fight disease. In examining and understanding at a molecular level how our body naturally fights diseases, we can then single out the cells that are doing the right thing and suppress any ‘James Bond’ cells that are aiming at the wrong target. This discovery could not have been achieved without cutting-edge technology that allows scientists to single out individual immune cells, rather than try to examine thousands at once. “We and others have been following this family tree from one daughter cell to the next to discover how each cell type is created and how the parent cell ‘decides’ if it should make more of itself or create the next cell type. By dissecting the heritage of these cells, we can find new targets to tackle a range of conditions including infectious diseases, cancers and immune disorders, and even make vaccines more effective,” says Dr Shalin Naik. Walter and Eliza Hall Institute has received $5.5 million in grants from the ACRF which has funded technology to progress research in lymphoma, breast, lung and genomics. The original article was published the Walter and Eliza Hall Institute for Medical Research website. To read the original article, please click here.
Tracking ovarian cancers’ evolution to change approaches to treatment Posted on June 3, 2015March 14, 2018 by Carly du Toit We often think of evolution as a positive thing, associating it with progress, growth and development. But because evolution exists in all living things, including cancer cells, it also presents one of the greatest challenges for researchers as they seek out new ways to outsmart an ever moving target. But thanks to the team of world-leading researchers at the ACRF funded Peter MacCallum Cancer Centre at least four evolutionary processes have now been identified that enable ovarian cancer cells to resist chemotherapy treatments. In collaboration with two other key ACRF-funded research institutes, University of Queensland’s Institute of Molecular Biosciences and Westmead’s Millennium Institute, the research team used whole genome sequencing to analyse tumour DNA samples from 91 patients with high-grade serous ovarian cancer. Their new insights into how these cells genetically change to become resilient will allow researchers to investigate more effective treatments – treatments that are tailored to break through each defensive barrier. The defence mechanisms identified in these cancer cells included everything from “hijacking” genetic switches that enable them to pump chemotherapy drugs out of their way to reshaping and accumulating “scar tissue” which appears to block the chemotherapy drugs. ‘In this research we saw stark reminders of how evolution presents us with incredible challenges – to fight an insidious enemy, you need to understand them, and we’ve made a great leap forward thanks to a truly international collaborative effort ,’ says Peter Mac researcher Professor David Bowtell. Before this clinicians would watch as initially effective treatment became ineffective and cancer cells made an aggressive comeback in their patients. For decades they had little information to guide them when selecting treatment for women whose cancer has returned. ‘The research is a turning-point in the global fight against ovarian cancer it offers great hope to patients world-wide,’ says Professor Bowtell. To date this has been the largest complete DNA analysis of ovarian cancer in the world and it would not have been possible without the outstanding support of ACRF donors. This information was originally published by the Peter MacCallum Cancer Foundation.
New melanoma treatment triggers 20-fold improvement Posted on April 17, 2015March 14, 2018 by Carly du Toit Studies conducted by cancer scientists at The University of Queensland Diamantina Institute (UQDI) have found a new experimental drug called Anisina significantly increases the effectiveness of existing therapies used to treat melanoma. Around 12,500 Australians are diagnosed each year with malignant melanoma and it is responsible for over 1,500 deaths. It is a notoriously difficult cancer to treat, due to the number of mutations that make the cancerous cells difficult to target. Errors in the ‘BRAF’ gene have been identified as among the most prominent mutations, and two drugs that target ‘BRAF’ (vemurafenib and dabrafenib) have been developed and approved for use in recent years. However no targeted therapy exists for the 50% of melanoma patients whose tumors do not have this most prominent mutation. As a result, developing a new drug that is effective across all mutations has become a focus in current cancer research. Cancer scientists have found that when Anisina is partnered with existing drugs it helps destroy two key parts of the cancer cell’s skeleton, resulting in a 20-fold increase in the anti-cancer effect of the other drugs. This benefits all melanoma patients fighting cancer as the new drug targets melanoma cells regardless of their mutational status. Nikolas Haass MD PhD conducted the research studies along with Brian Gabrielli PhD. Dr. Haass said, “These findings from the preliminary screen with Anisina are exciting. Finding a compound that is equally effective against a wide panel of melanoma cell types irrespective of the genetic background has been a long-held goal.” Justine Stehn PhD, Novogen Anti-Tropomyosin Program Director, said, ” The idea that we now have a means of making melanoma cells respond to potent anticancer drugs is an exciting development for patients with melanoma.” Plans are now underway to bring Anisine into the clinic by early 2016. The ACRF is proud to have provided $6.2 million to support the work of UQDI’s world-class researchers in recent years. This information was originally published by Novogen website and can be found here.
Discovery brings hope for new tailor-made anti-cancer agents Posted on April 25, 2013February 25, 2018 by Carly du Toit Researchers at the Walter and Eliza Hall Institute (WEHI) Melbourne have played a key role in developing a novel chemical compound which blocks a protein that has been linked to poor treatment responses in cancer patients. The development of this compound is an important step towards designing a potential new anti-cancer agent, which will help to significantly reduce resistance to therapy. The compound targets the function of a protein which prevents cells from dying. Cell death is an important safeguard against cancer development, but once cancer cells start growing, they can produce high levels of this protein which prevents this natural process. This also reduces the effectiveness of chemotherapy and other anti-cancer treatments, and has been associated particularly with poorer outcomes in patients with lung, stomach, colon and pancreatic cancer. Dr Guillaume Lessen (pictured) who co-led the study, together with Prof. Keith Watson and Prof. David Huang from the ACRF Chemical Biology Division at WEHI and colleagues Dr Peter Czabotar and Prof. Peter Colman, said: “We were very excited to see the team’s work culminate in a compound that specifically inhibits the protein.” Continue reading “Discovery brings hope for new tailor-made anti-cancer agents”
