Ferrier’s focus on the future
4 December 2015
Three different projects focused on solving a variety of problems, which are being led by scientists at Victoria University of Wellington’s Ferrier Research Institute, have been awarded a total of $3 million in Government funding to develop their commercial potential.
The Ferrier Research Institute specialises in carbohydrate chemistry and is focused on bringing better drugs, materials and other technology to the world.
The scientists, Professor Gary Evans, Dr Phillip Rendle and Professor Bradley Williams, are each receiving $1 million over two years from the Ministry of Business, Innovation and Employment (MBIE) through its Smart Ideas science investment round for 2015.
“New Zealand now has an incredibly competitive science funding system, with the smallest approval rates for proposals in the world. The major success by our Ferrier scientists and their research collaborators in this round speaks to the potential impact of the proposed projects and the quality of the ideas.”
Hope for Huntington’s
Dr Phillip Rendle’s research aims to produce a safe and effective treatment for some or all of the nine polyglutamine diseases, the most well-known of which is Huntington’s. These diseases are genetically inherited and rare, affecting around 1 in 10,000 people worldwide.
Dr Rendle says there is currently no cure for these diseases, just treatments for the symptoms, which typically emerge in mid-life and get progressively worse with age.
“I want to find a treatment using dendrimers, which are molecules that look like a heavily branched tree. Polyglutamine diseases are neurodegenerative diseases caused by the abnormal interaction of inherited mutated proteins. Our aim is to use dendrimers to disrupt this interaction to delay the onset age, which would effectively be a cure.”
Dr Rendle says he’ll be working with Professor Russell Snell from the University of Auckland, an expert in Huntington’s disease who will conduct biological testing of the materials being developed in the project.
Reducing infections from surgical implants
Professor Gary Evans is developing materials that will reduce infections which sometimes require orthopaedic implants—such as hip or other joint replacements—to be removed.
Biofilms are produced by microorganisms and form a protective layer that adheres to surfaces. In the case of orthopaedic implants, the majority of post-surgical infections are caused by bacteria growing within a biofilm, which develops on the implant. Where a biofilm is allowed to form, these bacteria are protected from the patient’s immune system and antibiotic treatments.
Professor Evans says he and his team (which includes researchers from Callaghan Innovation and University of Otago) will try to engineer entirely new materials through coating titanium, which is used in the majority of modern orthopaedic implants, with molecules that stop biofilm formation.
“While removal of a joint is only necessary in 1-2% of cases, when that’s applied to 3.7 million such surgeries a year in the United States alone, preventing those infections would have a big impact and save a lot of money,” he says. “As the population ages and expects to be more mobile with the help of joint replacements, the issue is only going to become more pronounced.”
A new kind of paint that would stop barnacles and other organisms from accumulating on the hulls of marine vessels has the potential to revolutionise the shipping industry, according to Professor Bradley Williams.
“The growth of seaweed, barnacles and the like on ships is a major problem for marine industries. It creates lots of resistance, which means slower ships and requires as much as 30% more fuel to maintain shipping speeds for on-time delivery—that’s hard on both the financial bottom line and the environment. The ships need to be dry-docked while the encrustation is removed, which takes time and money. And if a ship is wrecked, the biocides which are currently used in paints to ward off encrustation end up leaching into the ecosystem.
“Mine is an extremely simple idea that brings together existing scientific principles in a new way. But the way this idea intends to solve the problem and the fact it won’t have any impact on the environment means it has the potential to be a game changer for paint manufacturers in the shipping industry.”
The formula for teaching success
10 November 2015
"Every student has potential. The secret is to try to reveal the student's aptitude to themselves, to give them the confidence to help maximise that potential."
That’s the teaching philosophy of Dr Robert Keyzers, a Senior Lecturer in chemistry from the School of Chemical and Physical Sciences and a recipient of a Victoria University Teaching Excellence Award.
The awards recognise a consistently high level of teaching, reflected in both peer and student feedback, as well as ongoing innovation and leadership. "Keeping in mind the specific needs, and the background knowledge and understanding of students are key aspects to helping them on their academic journey. I try to do this by walking down the learning path with them.
“This is made easier by the fact that the subjects I teach are not necessarily 100 per cent connected to my own research. This can help with teaching because, without the complete background, I don’t necessarily know what the students don’t know at the beginning of a semester. As such, the process of discovery means I can look at the material with a similar viewpoint to them,” says Rob.
According to Rob, one of most rewarding experiences in teaching is seeing the “penny drop” with a student who has been struggling with a difficult concept.
“You can really see a gleam in their eyes as it all just clicks into place, which is a magical moment for any teacher.” Rob initially had a goal of becoming a forensic scientist. However, the realisation that he would face a limited job market in this field led him to eventually find a passion for the chemistry of nature.
His research includes bio-prospecting from marine organisms around the Pacific to identify new pharmaceutical compounds for medical applications. He also studies the compounds important to the sensory properties of wine to explore how they can be optimised.
He spends much of his time teaching for programmes, such as biology and geology, but also strives to instil a love of chemistry in students as well.
Rob says the award is a good reminder of the importance of teaching at a tertiary level.
“Teaching is the central core of what a university is about, but I think we, as academics, can often get distracted by the excitement of our research. Awards like this remind us of the importance of nurturing the younger generation of future academics and professionals as they set out on their career path.”
Copying tuberculosis could yield vaccines against malaria and cancer
5 August 2015
Future vaccines might one day contain a tiny whisker of tuberculosis, to boost their power.
Victoria University chemists Bridget Stocker and Mattie Timmer's research into tuberculosis may eventually form part of a vaccine for malaria, one of the biggest challenges for medical researchers today.
One of the difficulties they face is in hitting the right note between the body overreacting or underreacting, Timmer said. "Too much can be dangerous."
But underreacting to a vaccine means the body's immune system "memory" of the disease will be weaker, so immunity will not last as long. Something added to a vaccination that will make the body sit up and take notice – and keenly remember – would be a valuable tool for health researchers.
The Marsden-funded pair believed a chemical, found on the little-studied outer surface of the tuberculosis bacterium, might be just such a tool, Timmer said.
People are born with their immune systems primed to recognise this surface and fight the disease – once the leading cause of death in the Western world, infecting the lungs, lymph nodes, bones, joints and kidneys.
"We can find out what those [chemical] structures are, and then make them, and make modifications to see if we can improve the activity."
Stocker and Timmer would spend about three years creating and testing sister chemicals of this tuberculosis molecule. Their aim was strike a balance between something that effectively activated the immune system but was also simple to make, he said.
The final product would be inspired by the tuberculosis chemistry, but made from scratch in the lab before being included in the vaccine, Stocker said. "It might freak people out, but all we're doing is looking at the molecules on the outside of the bacteria."
The chemical has none of the infection-causing parts of tuberculosis, so no one would be at risk of developing the disease should it be included in a vaccine, Timmer said. "The vaccine can be against anything: pathogens and bacteria and anti-cancer vaccines."
Through her work, Stocker had seen the fears that small numbers of people had about the safety of vaccines. While all would be subject to thorough, independent safety tests, she wondered if a product derived from a "natural" source might be accepted more easily by a chemical-averse public.
"People assume because it's natural it's better. But it's just a perception."
One of the first uses of the research might be in a planned vaccine for malaria, Stocker said. "It was why I got into science – to be able to contribute something."
Ferrier science embedded in biotech drug development
28 July 2015
A new drug developed to treat a debilitating rare muscle-wasting disease and various kidney diseases, and manufactured using Ferrier Research Institute technology, has been acquired by an American company for commercial development.
New Zealand Pharmaceuticals Limited (NZP) announced last week that the Patent License and related Agreements for DEX-M74 has transferred to Altamira Bio, a subsidiary of NASDAQ-listed Fortress Biotech, who will run the clinical development and commercialisation.
DEX-M74, a natural carbohydrate, is currently in a Phase 2 clinical trial for treatment of the rare genetic disorder GNE myopathy, and a Phase 1 trial in patients with kidney disease is scheduled to begin in September.
GNE myopathy, formerly known as Hereditary Inclusion Body Myopathy, is a severe debilitating muscle wasting disease afflicting approximately 2,000 people worldwide. Most patients develop weakened arm, hand and leg muscles in their early 20s and eventually require a wheelchair.
“This is a significant milestone. NZP manufactures DEX-M74 using technology developed and licensed from Ferrier”, says Director of the Ferrier Research Institute Professor Richard Furneaux.
“In fact, the late Professor Robin Ferrier, after whom our Institute is named, was instrumental in developing the manufacturing process when he worked with us in his retirement.”
DEX-M74 has the potential to supplement the patient’s genetic insufficiency by restoring the sialic acid content of their diseased tissues to natural levels.
“Low sialic acid levels are also a feature of many major kidney diseases, so there is cautious optimism that it will have broader applications”, says Professor Furneaux.
Professor Furneaux says Palmerston North-based NZP is going from strength to strength. “We have had a long and productive relationship with NZP. Their Business Development Manager Dr Selwyn Yorke, who has championed the development of DEX-M74, was member of our research team at one point.
Marine sponge shows tumour-stunting promise
7 July 2015
A chemical agent found in marine life unique to New Zealand may hold the secret to fighting certain cancers, according to research co-authored by Victoria University of Wellington’s Professor John Miller and associate professor Peter Northcote.
The research, which has been published in the highly-regarded journal Molecular Cancer Therapeutics, suggests that peloruside A—a substance produced by the marine sponge Mycale henscheli, found mostly in Pelorus Sound—has promising tumour-inhibiting properties when compared to other plant and bacterial-based agents currently used in chemotherapy.
One preclinical trial on lung cancer cells showed tumour growth inhibition greater than 90 per cent with peloruside A, compared with results of 53 per cent and 19 per cent for two current anti-cancer drugs.
A similar preclinical trial on cells of a different type of lung cancer also produced encouraging results, with inhibitions of tumour growth ranging between 50 to 74 per cent, compared to 44 and 50 per cent with the alternatives.
Tests were also conducted on breast cancer cells, with the results suggesting better toleration of peloruside A than the clinically used drugs.
“Although additional research is required, the preclinical results certainly suggest that peloruside A is highly effective in preventing the growth of lung and breast tumours,” says Professor Miller.
“In some cases, there was even a decrease in tumour volume.”
The research also indicates that peloruside A may provide an answer to the growing problem of the acquired resistance of some tumours to current medications.
“This is encouraging, because it means peloruside A could increase the range of options available for long-term treatments; particularly if there are fewer side effects with peloruside A compared with drugs currently used to treat cancer,” says Professor Miller.
Professor Miller believes the results give strong support for further trials. However, advancing clinical studies is challenged due, in part, to a limited supply of the marine sponge.
Efforts are underway to provide enough material, either from aquaculture or large-scale chemical synthesis, to commence human trials.
The research was conducted in association with colleagues from the University of Texas Southwestern Medical Center, Reata Pharmaceuticals, and the CTRC Institute for Drug Development.
You can hear more from Professor John Miller below:
Funding to research cancer treatment
7 July 2015
A Victoria University of Wellington PhD student has received a 2015 Todd Foundation Award for Excellence.
Abigail Sharrock from the Centre for Biodiscovery and School of Biological Sciences has been awarded $5,000 for her research project which seeks to understand how tiny biological machines called nitroreductase enzymes can activate anti-cancer drugs for new cancer therapies.
Abigail aims to develop an improved treatment technology with fewer side-effects to provide cancer sufferers with a better quality of life and a much better prognosis. Her research will also have applications in regenerative cell biology studies. Her PhD is supervised by Dr David Ackerley.
Among the other award winners around the country include research projects on alleviating pressure on stormwater networks, improving the performance of seismic energy dissipation mechanisms during earthquakes and developing a real-time cardiac MRI tracking technique.
Applications for the 2016 Todd Foundation Awards for Excellence close on 1 March next year.
E-cigs with nicotine could help women quit smoking - NZ research
16 June 2015
Electronic cigarettes with nicotine could be a useful tool in helping women, in particular, quit or reduce tobacco smoking, New Zealand research suggests.
But the required nicotine-containing liquid was not legally for sale in this country, although electronic cigarettes were, said study co-author Professor Randolph Grace from the Canterbury University Psychology Department.
Some people were ordering the nicotine e-cigs online from a website in China, but many economically disadvantaged people were unable to do so because they did not have credit cards.
The lack of a credit card particularly affected Maori and Pasifika, who were about twice as likely to smoke as other groups, Grace said.
The researchers provided 357 New Zealand smokers who had no intention to quit with a sample of a nicotine e-cig during interviews in November and December 2012.
Overall, participants rated the nicotine e-cigs to be 83.3 per cent as satisfying as their own-brand tobacco, but for women the figure was 91 per cent, while for men it was 74 per cent.
There were 227 participants who agreed to be re-interviewed in February and March 2013, following a 10 per cent rise in tobacco tax. Of that group, 37.8 per cent said they had cut back or made a change in their smoking habit, while 7 per cent had quit.
Most of the reasons given by participants for smoking less were economic, but those who had cut their smoking were also those who had a more favourable impression of the nicotine e-cigs, Grace said.
Perhaps those wanting to quit or cutback were more likely to see the e-cigs as an attractive potentially healthier alternative.
One reason the nicotine e-cigs could be particularly useful for women was that nicotine replacement therapies, such as patches or gum, were less effective in helping women reduce tobacco smoking than men.
"It seems as if the physiological aspect of nicotine addiction is relatively more important in maintaining smoking for men. For women there's relatively more importance for the contextual factors, the behaviour," Grace said.
With e-cigs, people could continue to take part in the behaviour of smoking.
Very strong evidence indicated e-cigs were less harmful than tobacco. The carcinogens in smoking did not come from nicotine but from the burning of tobacco and additives.
Grace said some researchers, including himself, felt a harm minimisation strategy would allow smokers to legally buy nicotine e-cigs in this country if they wanted to quit smoking.
Other researchers, including some practitioners in the addiction field, were against the legalisation of nicotine e-cigs because of concerns young people could become hooked on them.
In his view nicotine-containing electronic cigarettes should be legal for sale to smokers who wanted to use them to quit or reduce the amount of tobacco cigarettes they were smoking, Grace said.
"I wouldn't legalise them open slather because there is a potential for young people to get addicted to nicotine."
Other co-authors of the study were Dr Bronwyn Kivell from the School of Biological Sciences at Victoria University and Dr Murray Laugesen from Canterbury University and Health New Zealand.
Victoria researcher wins funding for revolutionary research
5 June 2015
A Victoria University of Wellington biology researcher has been awarded over $1 million dollars in funding for a revolutionary research project that will “rewrite the textbooks” and could change the way we treat cellular diseases such as brain cancer and Alzheimer’s.
Dr Melanie McConnell says she was nearly speechless when Health Research Council of New Zealand announced it will provide $1,036,746 to fund her three-year project.
“It is very, very exciting. It secures funding to get a team of people working on my research, and allows them to put their heads down and get on with it. Without the grant, the project wouldn’t happen,” she says.
Dr McConnell says the project is based on a discovery made five years ago during her time at the Malaghan Institute of Medical Research, which is based at Victoria University, and was further developed during her current post at Victoria.
The project centres on the discovery that mitochondria can move between cells.
“It’s a new observation that goes against all the dogma in the textbooks. At first, people refused to accept our data. We’ve always assumed mitochondria have to renew themselves within the cell, but the research conducted at Malaghan with Professor Mike Berridge shows that mitochondria can transfer between cells.
“This is potentially a double-edged sword. Cells that are injured in neurodegenerative diseases could use mitochondrial transfer to survive, but cancer cells could also use this process to resist treatment,” she says.
The outcome of her research could change how we treat neurodegenerative diseases such as Alzheimer’s, Parkinson’s and motor neurone disease, where injured brain cells die, and also brain cancers where injured cells are actively growing and resist attempts to kill them.
Dr McConnell will lead the project’s team of five throughout the three-year research period.
“This is only the first step of what could be a 15-year project. Our ultimate goal is to hack the
body’s mitochondrial transfer system to alter cell survival in disease.”
For more information contact Jolene Williams on 04-463 6385 or email@example.com
New company to advance potential treatment for cancer and other diseases
21 May 2015
Equity investment for the company, called Avalia Immunotherapies, is coming from New Zealand investment firm Powerhouse Ventures, the New Zealand Venture Investment Fund, Malcorp Biodiscoveries Limited and Victoria Link Limited (Victoria University’s commercialisation office). Additional support is also coming from Callaghan Innovation’s technology incubator programme, in the form of a repayable grant, and the Kiwi Innovation Network.
The director of the Ferrier Research Institute, Professor Richard Furneaux, says Avalia Immunotherapies will further develop the ground-breaking technology and aims to progress it to clinical trials.
The research has been led by Dr Gavin Painter from Ferrier Research and Dr Ian Hermans from the Malaghan Institute, and works as a therapeutic vaccine, activating a patient’s own immune system to recognise and attack cancer cells.
Avalia Immunotherapy’s chief executive, Dr Shivali Gulab, says the decade-long research partnership between Dr Hermans and Dr Painter has led to a powerful technology platform that has
been patented and licensed to the company for commercial development.
“The technology can be used to design new treatments for cancer, as well as infectious disease and allergy. Our initial focus will centre on cancer immunotherapy.”
Professor Furneaux says the potential benefits of the therapy are huge, not only for cancer patients but for the Wellington research community. “I’ve worked in this field since 1980 and this is the first time I’ve been involved in placing our intellectual property in a New Zealand start-up company—that’s how important this research is.
“This is also the beginning of what we hope is a birth of a biomedical initiative for the Wellington region—there’s fantastic biomedical infrastructure here, from research facilities to the excellent District Health Boards. We’re hoping Wellington will become just as well known for its biomedical research as it is for its film industry.”
For more media coverage:
World first discovery
30 April 2015
In the first week of January, Malaghan Cancer Cell Biology Group Leader and Centre for Biodiscovery member Mike Berridge and his team, working on breast and melanoma cancer models, discovered that DNA moves from surrounding normal cells to tumour cells with defective mitochondrial DNA.
Senior Research Officer Carole Grasso’s beautiful images highlighting the transfer of fluorescent mitochondria across nanotube membrane connections between cells have been reproduced internationally.
This research opens new possibilities for controlling tumour growth and spread throughout the body. The research could lead to new approaches to treat cancer; to encourage mitochondrial transfer to tumour cells with damaged mitochondrial DNA, and to encourage mitochondrial respiration which discourages tumour growth. Like many discoveries scientists make while investigating one disease, there are implications for another; it may be that this new understanding also offers future treatments for neuromuscular and neurodegenerative diseases involving the sensory organs, and even ageing.
Mike has just visited his co-leader Professor Jiri Neuzil of Griffith University in Queensland and says their publication has opened several new opportunities for collaboration with scientists at the Pasteur Institute in Paris, Virginia Commonwealth University in the USA, the Garvan Institute in Sydney and with others closer to home.
New approaches to breast cancer
30 April 2015
Cancer research at the Malaghan Institute operates on several fronts with many intersecting approaches seeking breakthroughs and moving us closer to new treatments or cures thanks to the committed support we receive.
PhD student Connie Gilfillan is investigating Doxorubicin - a chemotherapy which has been used in the treatment of breast cancer for over 30 years - and investigating the role of dendritic cells in tumours.
“In 1984 Doxorubicin was approved, and while it’s an effective treatment, it shares the fate of many cancer drugs; tumours become resistant to them. I wanted to find out whether the treatment leaves carcinoma cells more immune suppressive after ‘chemo’, or less able to respond to the immune system.”
Immunotherapy hopes to unlock the body’s own fight against cancer; but because cancer cells have incredible dexterity in eluding or hiding from the immune system, they are usually not detected and destroyed. If they are even less likely to be targeted after ‘chemo’ we need to find out additional ways to wake up the immune system.
“Dendritic cells, DCs, are the communicators of the immune system. They are a kind of first alert cell which notices something amiss and then travels back to the lymph nodes to get specialist cells to help. There are many ways that I am testing and probing their role. For example if I take them out of the system completely what happens? Or, if a tumour is immune suppressant does the presence of DCs make things better or worse?” says Connie. “While there is genuine excitement about what we are learning about the various immune cells, there are easily over a hundred to investigate and every small thing discovered adds to the big picture. I look at it like a family tree; the B Cells, the T cells and DCs are at the head of the family but they have a whole family of cells under each, branching out in complexity. I am only looking at one cell and that may occupy me for three years! It is an amazing area of research and the Malaghan Institute is an incredibly stimulating place to be.”
Connie is one and a half years into her PhD under supervisors Professor Franca Ronchese, Dr Melanie McConnell (Centre for Biodiscovery), and Professor Brett Delahunt (Otago).
Hookworm: The Great infection of Mankind, discovery at Malaghan Institute
27 April 2015
In 1962, Norman Stoll, the distinguished Rockefeller Institute scientist who helped to establish human parasitology research in North America, described Hookworm as the Great Infection of Mankind.
Professor Graham Le Gros has led a team which has stimulated both innate and memory responses to the parasite, discovering along the way the unexpected behaviour of one particular immune cell, in Hookworm, one of the world’s most devastating tropical diseases affecting 1 billion people. The journal, Nature Communications, has today published the research  .
Ten years of work has seen the Wellington-based scientists demonstrate the interaction between innate and adaptive immune cells, never seen before, providing a credible platform for researchers to work towards preventing a disease that causes global suffering.
Hookworm affects mostly the poorest billion people in the world and, according to the World Health Organisation, contributes to the cycle of poverty and ill health for communities of people living on less than $2 a day. Hookworm infection causes childhood and maternal anaemia, wasting, pain, disability and impaired brain development, but has proved impossible to eradicate as rates of reinfection are high.
Hookworms reproduce in the gut and the eggs passed in stools. The cycle of reinfection continues in poor communities where the lack of both sanitation and footwear makes eradication impossible. The most feasible way to break this cycle would be to create a vaccine for protective immunity but before we can start developing a vaccine against the parasite however, we first need to identify the immune mechanisms that can best protect against hookworm infection.
Graham Le Gros explains, “Humans have evolved to develop immunity to many parasites, but not Hookworm. An unusual feature of their life cycle is that it includes migration of the larvae to the lungs before they develop into adults in the gut.
We were able to create an immune response in the lungs of mice that made it hard for the parasite to live – and therefore break the lifecycle. Our hunt is now to find the right hookworm protein to combine with an adjuvant triggering the activation of these immune cells - to teach a human body to have a memory of how to fight Hookworm.”
Additionally, the team demonstrated one immune cell - type 2 innate lymphoid cells ( ILC2s) - trigger immunity and work with other immune cells, the Macrophages and T helper cells. Previously ILC2s were not thought to be involved as an effector cell in long term memory response to fight off the disease.
The research was assisted by synthetic chemist Dr Gavin Painter from the Ferrier Research Institute and Centre for Biodiscovery at Victoria University of Wellington. The Ferrier Institute are regular collaborators with scientists from the Malaghan Institute. The work was funded by the Health Research Council of New Zealand.
The Centre for Biodiscovery and the Malaghan Institute of Medical Research present Dr Catherine Drummond
Department of Oncology, St Jude Children’s Research Hospital, Memphis
Finding new targets for cancer therapy
Wild-type p53 is expressed by approximately 50% of all tumours at diagnosis and is often accompanied by aberrations in upstream signalling pathways. Reactivating p53 is an attractive treatment therapeutic strategy in these tumours and disrupting the interaction between p53 and its negative regulator MDM2 has been a particular focus. However, as with other targeted therapies, resistance and relapse following treatment is likely. There is a need to both understand how resistance to small molecule activators of p53 might develop in a clinical setting as well as identify alternative ways in which these tumours can be selectively targeted.
Research conducted in the Lunec Lab (Northern Institute for Cancer Research, UK) was aimed at understanding how resistance to MDM2/p53 binding antagonists might arise. Two independent cell lines with resistance to chemically distinct classes of antagonists were generated and following detailed characterisation found to have identical TP53 mutations. These mutations were found to be present at low frequency in the parental populations, suggesting that these mutations were selected for during exposure to low concentrations of the antagonists. However, as these cell lines remained sensitive to ionising radiation these results also suggest that in a clinical setting, patients might respond to conventional chemotherapy.
Identifying alternative ways of targetting tumours expressing wildtype p53 was the the focus of work conducted in the Lain Lab (Karolinksa Institutet, Sweden). 20,000 small molecules were screened in a cell based p53 activation assay in order to identify bioactive compounds. MJ05 was one of the top hits identified in this screen, and was found to have cytotoxic effects in ARN8 melanoma cells (sub-G1 fraction of 16%) whilst having little effect on human normal dermal fibroblasts. MJ05 was subsequently found to be inhibiting S phase progression and, unlike other inhibitors of S-phase, did not activate or inhibit DNA damage response pathways. Whilst these effects of MJ05 were p53 independent, MJ05 also selectevly increased the cytotoxicity of the MDM2/p53 binding antagonist nutlin-3 (from 1.5% to 64%), suggesting utility in both p53 wildtype and mutant tumours.
More recently, studies in the Hatley Lab (St Jude Childrens Research Hospital, US) have been focussed specifically on a transgenic mouse model of embryonal rhabdomyosarcoma (ERMS). ERMS is a soft tissue malignancy that, despite being predominantly p53 wildtype, is observed clinically to express a diverse range of mutations. Furthermore, the origin of these tumours is unknown making the development of targeted therapeutics difficult. Lineage tracing studies in this mouse model are currently in progress, and whilst still ongoing highlight the potential for target discovery in transgenic models.
Tuesday 5 May 2015, 12pm - HMLT104
Chemists make headway in Alzheimer's research
Victoria University of Wellington researchers have made a significant step forward in the search for a treatment for Alzheimer's disease.
Chemists at the Ferrier Research Institute have discovered a way to create cluster compounds for controlling the process that leads to generation of amlyloid plaques in the brain disease.
In 2013, the chemists synthesised a type of complex sugar for the same purpose, in challenging 55 step synthesis. The new approach to construct single-entity clusters reduces the number of reaction steps by half.
“We wanted to simplify the synthesis without losing the desired potency, which is quite challenging,” says project leader Dr Olga Zubkova. “The new products will be easier and cheaper to make, and allow us to prepare larger amounts for various testing.”
Through the joint project, Ferrier chemists Dr Zubkova and Professor Peter Tyler worked with Professor Jeremy Turnbull and Dr Scott Guimond from University of Liverpool to construct new heparan sulfate glycomimetics with critical functions that control the activity of the beta-secretase enzyme in the brain. This enzyme catalyses the first step in the generation of amyloid plaques in Alzheimer’s Disease.
“We designed and decorated a more simplified dendritic core by using multiple short, more readily synthesised fragments”, says Dr Zubkova. “Though we significantly simplified the structures we still saw impressive amounts of bioactivity.”
Dr Zubkova says this provides a highly desirable product that could be used in the development of new treatments.
“These molecules involve sophisticated chemistry processes and target enzymes extremely well, which is crucial for pharmaceutical application. It could be used in numerous treatments as the role of heparan sulfate becomes better understood.”
The research, published recently in prestigious international journal Angewandte Chemie, was supported by funding from the Ministry of Business, Innovation and Employment.
The team has prepared a large collection of the compounds, with approximately 80 new intermediates as well as 11 final products as pure single molecules, something not previously achieved by any research group in the world.
“Others have tried by attaching highly charged fragments to the core which leads to a very complex mixture”, says Dr Zubkova. “But we’ve done it differently—we attach the fragments first before we sulfate them. We have, for the first time, prepared single-entity compounds presenting polyvalent display of heparan sulfate saccharides. That’s a point of difference and what makes our compounds unique.”
The Centre for Biodiscovery, the Malaghan Institute of Medical Research and the Maurice Wilkins Centre for Biodiscovery present Dr Jill O'Donnell-Tormey, Ph.D.
Chief Executive Officer and Director of Scientific Affairs
Cancer Research Institute, New York
Cancer Immunotherapy: A Not-For-Profit Vantage Point
Cancer immunotherapy, a class of treatment that harnesses the immune system's power to target and eliminate cancer, has recently enjoyed a renaissance of interest thanks to significant clinical successes. Several active immunotherapies have received FDA approval, and many more are making their way through the clinical development pipeline. The Cancer Research Institute (CRI), a U.S.-based charity that is dedicated exclusively to advancing immunotherapy for all cancers, is playing a critical role in the discovery, development, and optimization of cancer immunotherapies, especially combination approaches that bring multiple drugs together to achieve maximum clinical benefit. In this talk, we will review CRI's model for philanthropic innovation and discuss how it may provide a roadmap for rational and efficient development of immunotherapy across industry and academia.
Jill O’Donnell-Tormey, Ph.D., is Chief Executive Officer, and Director of scientific affairs of the Cancer Research Institute (CRI), a nonprofit organization founded in 1953 that is today the global leader in supporting and coordinating research aimed at harnessing the immune system’s power to conquer all cancers. She joined the organization in 1987 as director of scientific affairs, and has been chief executive since 1993.
Prior to joining CRI, she served as a research associate in the department of medicine at Cornell University Medical College and as a postdoctoral fellow in the laboratory of cellular physiology and immunology at The Rockefeller University. She holds a Bachelor of Science degree in chemistry, summa cum laude, from Fairleigh Dickinson University, and a doctor of philosophy in cell biology from The State University of New York’s Downstate Medical Center.
For more information about the Cancer Research Institute, please click here
Refreshments will follow the lecture
All interested parties are welcome to attend
Please RSVP to Charlotte Ansell at firstname.lastname@example.org by Friday 27 February
2015 Ferrier Lecture
The 2015 Ferrier Lecture will be given by Professor Larry Overman from the University of California, Irvine at Government Buildings, Wellington, onTuesday 3 March.
Professor Overman will also give lectures to the NZIC Otago Branch in Dunedin on Wednesday 4 March and the NZIC Auckland Branch on Monday 9 March. Times and venues for these events will be advised in due course.
Title and abstract
Natural Products Synthesis: Insights into Chemical Reactivity and Inspiration for New Antitumour Agents.
Progress in organic chemistry has been closely linked to natural products since Serturner’s isolation of pure morphine in 1803 and Woehler’s conversion of ammonium cyanate to urea in 1828.
This lecture will describe two recent natural products total synthesis projects in the Overman laboratory, one that led to new strategies for coupling complex molecular fragments and another to a new class of preclinical epigenetic antitumor agents.
About the Ferrier Lecture
It was Robin Ferrier’s particular belief that young chemists could benefit greatly from mixing with leaders in their field. Therefore, invited Ferrier Lecturers, who are recognised internationally in chemistry or a related field, are brought to New Zealand to engage with postgraduate students as well as lecture.
The Ferrier Lecture is supported by private donors, including Dr Peppi Prasit (one of Robin’s former PhD students), as well as the New Zealand Institute of Chemistry (NZIC) and the Faculty of Science at Victoria University.
Despite failing health, Robin attended the inaugural Ferrier Lecture, given by Professor Vern Schramm in March 2013, but died later that year.
Kiwis help with lab-grown retina
4 February 2015
In what sounds like a gruesome sci-fi plot, Victoria University researcher David Ackerley is preparing to grow an artificial retina.
The biotechnologist, and others in a world-leading international team, hope it could help to cure one of the most common forms of vision loss.
The retina is a layer of light-sensitive cells at the back of the eye, connecting to the brain and allowing us to see. Though its cells consistently regrow themselves, this is an imperfect process - and some people are genetically predisposed to more frequent damage or the repair going astray, leading to degenerative blindness.
The "retina in a petri dish" will be grown from stem cells at Johns Hopkins University in the United States. Ackerley's team at Victoria and a second at Johns Hopkins will act as chefs, designing the ideal DNA recipe.
Having successfully grown a prototype healthy one, their next step is to make an unhealthy one that mimics degenerative blindness.
"Now you've got it working, the question is how do you make it stop working in a way that mimics degeneration [of vision]," Ackerley said. "The key thing is you want to leave most of the retina intact."
The international team has been given a US$500,000 (NZ$684,000) grant for this work.
The trick to knocking out specific visual cells was to add instructions to their DNA that made them die when exposed to an otherwise-harmless substance, leaving the cells around them unharmed.
Ackerley, with the Auckland Cancer Society Research Centre, is currently studying how transporting such DNA recipes into cancer cells could become a revolutionary new treatment. His team's experience in this made him ideally placed to join the international research.
Once they have grown the new retina, they will begin first by killing cells, then seeing what medicines help the retina to repair itself.
"I wouldn't say we've got a cure for blindness . . . It allows you to look in a way that can't currently be done for new drugs."
The example could be followed for studying diseases in other organs as well.
"This is a great system for just being able to look at the cells without harming any animals, and actually looking at the human response."
Bacteria and human cells can have a vastly different reaction to a substance - it's why when taking an antibiotic the drug will kill bacteria without affecting us.
David Ackerley's DNA recipe instructions borrow from the bacteria cookbook, specifically the steps to make a certain enzyme. The original enzyme converts an otherwise-harmless substance into a toxic one, poisonous enough to kill a cell. Ackerley's lab has since turbo-charged it, making the enzyme highly efficient.
By inserting these instructions into the same page of the cookbook as the recipe for a visual cell means just these specific cells will use them.
Therefore, when the harmless substance is added to the artificial retina, the light-receptive cells will make the toxin while the recipe will stay inert and unused in all other cells, which will live.
- The Dominion Post
US funding to research retinal disease
29 January 2015
Dr David Ackerley, from Victoria University’s Centre for Biodiscovery, is part of a team awarded a US$500,000 Falk Medical Research Trust grant to develop new models of retinal degenerative disease—–a major cause of human blindness.
Dr Ackerley will work alongside Dr Val Canto-Soler and Dr Jeff Mumm from the Johns Hopkins University in Maryland, USA, to build an artificial retina of the human eye that mimics degenerative disease.
“My lab group will be developing genetic methods to enable very precise killing of specific cells in the artificial retina to permit study of how they regenerate, and facilitate discovery of drugs that assist with this process,” says Dr Ackerley.
Dr Val Canto-Soler recently developed world-first methods to induce human stem cells to grow into an artificial retina in a Petri dish.
Dr Ackerley has previously collaborated with Dr Mumm to create a system for effectively killing specific living cells without harming surrounding tissues, using specially engineered enzymes.
The Falk Medical Research Trust grants one year of funding to find new cures for diseases or improve existing treatments.
Biodiscovery scholar cleans up prizes
26 January 2015
Last month, Cameron Field won the Student Poster Prize at the Australasian Society for Immunology’s (ASI) widely attended and stimulating annual scientific meeting. The week-long conference, in New South Wales, was attended by Nobel Laureate Bruce Beutler. Together with Jules A. Hoffmann, he received one-half of the 2011 Nobel Prize in Physiology or Medicine, for ‘their discoveries concerning the activation of innate immunity’. Ralph Steinman was awarded the other half of the Nobel Prize post-humously for his discoveries concerning the activation of adaptive immunity.
Dr Beutler was guest presenter at the conference’s Post-Graduate workshop which challenged attendees to solve their own immunological puzzles; a highly relevant challenge for Cameron and his peers.
Cameron’s poster, part of his PhD project, investigates immunotherapy possibilities for Glioblastoma multiforme (GBM), a rapidly fatal brain cancer, currently with limited treatment options. The poster win came less than a week after he received the runner-up Emerging New Investigator award, presented annually by the Wellington Health and Biomedical Research Society. The term new investigator is not related to chronological age but recognises substantial research endeavours started within the previous five years.
He shares his enthusiasm and determination to further our understanding of GBM, “Many tumours are good at side-lining or suppressing the immune system, and GBM has proved harder than most, but my study involves combining drugs to limit this suppression, with a vaccine.”
“A new class of drugs called ‘checkpoint inhibitors’, recently approved by the US Food and Drug Administration (FDA), are designed to block the inhibitory signals within the immune system that apply the ‘brakes’ to an immune response. When we cut the brake lines, we are able to unleash a more powerful immune response.”
Immunotherapy and cancer have become increasingly used in the public domain since the journal Science named cancer immunotherapy its 2013 Breakthrough of the Year, but a body of academic work, over several decades led to this public ‘tipping point’.
New Zealand and Australia; traditional rivals, joined forces 24 years ago to form The Australasian Society for Immunology, encouraging and supporting the discipline of immunology in our region and introducing young scientists to the discipline. ASI members have been prominent in advancing biological and medical research worldwide.
South Auckland-born Cameron, hopes to complete his PhD this year and join the growing list of New Zealand born scientists making their mark internationally. “By the end of the year I hope to complete my PhD. It’s been fantastic working at the Malaghan Institute for the last three years, under the supervision of Ian Hermans. “Both Ian and the Malaghan Institute command a high standard of research and this bodes well with our presence both nationally and internationally. Being challenged in this manner will more than prepare me for a research career ahead.”