Bosch Institute News 2012
30TH OF NOVEMBER 2012
Congratulations to Renae Ryan for receiving a Tall Poppy Award last night.
The following is an excerpt from the website of the Australian Institute of Policy and Science:
The Tall Poppy Campaign was created in 1998 by the Australian Institute of Policy and Science (AIPS) to recognise and celebrate Australian intellectual and scientific excellence and to encourage younger Australians to follow in the footsteps of our outstanding achievers. It has made significant achievements towards building a more publicly engaged scientific leadership in Australia.
The Tall Poppy Campaign currently recognises the achievements of Australian scientists through the prestigious annual Young Tall Poppy Science Awards and the biennial CSL Florey Medal.
The Campaign’s Tall Poppies Reaching Students Program engages the winners of Young Tall Poppy Science Awards (‘Tall Poppies’) in activities to promote study and careers in science among school students and teachers as well as an understanding and appreciation of science in the broader community.
by Prof. Robert Vandenberg
A New Form of Toxic Rust Discovered in Patients with the Crippling Neural and Cardiac Disease, Friedreich’s Ataxia
30TH OF NOVEMBER 2012
The crippling disease Friedreich’s ataxia is probably one of the most destructive conditions that can inflict young children and teenagers. It attacks both the nervous system and the heart and leads to the child being confined to a wheel chair early in life and there is currently no treatment.
However, recent studies by an international research team, led by Professor Des Richardson at the Bosch Institute and Department of Pathology, University of Sydney, could hold a clue in both understanding the condition and developing new therapeutics.
In a very recent study published in the Proceedings of the National Academy of Sciences USA, Richardson and his colleagues have uncovered that an accumulation of an iron rust within the part of the cell that generates energy (the mitochondria) and could be important in the damage observed in both the heart and nervous system.
It has long been known that accumulations of toxic iron in tissues can cause severe damage, but this new form of iron is something quite different to that observed previously and has the potential to be extremely toxic. In fact, its an iron rust somewhat different to what you find on car bumpers, but its location within the site of the cell that generates energy (known as the mitochondrion) is of great concern. Generally, iron that accumulates in tissues is protected by a special protein called ferritin. This new rust has no protective shell and is probably very toxic because of that.
The team is currently aiming to develop a new therapy that prevents the accumulation of the “rust” and restores normal function, which would be an important step in treating Friedreich’s ataxia.
19TH OF NOVEMBER 2012
In a breakthrough for both nanotechnology and multiple sclerosis, biodegradable nanoparticles have been used to deliver small proteins to the spleen that makes the immune system stop attacking the nervous system’s myelin in multiple sclerosis. Professor Nicholas King, Head of the Discipline of Pathology at the University of Sydney, and Professor Stephen Miller at Northwestern University in the USA, have used this novel approach to stop multiple sclerosis in mice. “This could feasibly be used to halt other autoimmune diseases, also,” Professor King said, “although we still have many experiments to do to confirm this. This is a real coup for translational research!” The paper reporting this work has just been published online in the prestigious journal Nature Biotechnology.
Professor King, a member of the Bosch Institute, which has supported this work over many years, has been working on this nanotechnology approach for the last 6 years in several models. Dr Daniel Getts, a former PhD Student in Professor King’s lab who co-discovered the modulating effects of these nanoparticles with Professor King and who is first author on this paper, decided to apply the principles he had discovered at the University of Sydney during his Post Doctoral fellowship with Professor Miller at Northwestern University in Chicago. Professor Miller is internationally known for his contribution to the understanding of multiple sclerosis using animal models. Dr Rachael Terry, who completed a PhD in Professor King’s lab earlier this year working on this project, is also doing a Post Doctoral Fellowship in Professor Miller’s lab and contributed significantly to this work. This novel technology could theoretically be applied to a variety of autoimmune diseases such as Type 1 diabetes, but potentially also for other immune-mediated diseases, such as food allergy and asthma.
In multiple sclerosis, cells of the immune system suddenly recognize and destroy the delicate covering of myelin that covers nerve cells and enables them to transmit electrical signals. What causes it is unknown. In humans, this debilitating disease causes symptoms that vary from mild limb numbness to paralysis, as well as blindness, causing major suffering. The disease comes in waves, frequently relapsing and remitting for many years.
To date, immunosuppressant therapy to control multiple sclerosis has been variably successful but has always been a double-edged sword. When you suppress the immune system, you remove the ability of the body to fight off infectious organisms and destroy emerging cancers.
The investigators injected small myelin proteins attached to nanoparticles 500 nanometers in diameter into the bloodstream. The nanoparticles went to the spleen where they were taken up by arrays of cells there called macrophages, which are able to engulf any debris that goes by via “scavenger receptors” on their cell surface, thus removing it from the body. These macrophages normally get rid of old and dead cells from the body. However, in doing so it is thought that they also send local signals into the surrounding spleen (where immune responses are often first generated) that tell the immune system not to respond to the proteins from these broken down ‘self’ cells to prevent autoimmune responses. Once taken up by these macrophages, the ultimate effect of the nanoparticles is to suppress the immune response to the myelin proteins directly and also increase the number of regulatory T cells that damp down this response. This new approach thus does not cause blanket immunosuppression, but induces a specific tolerance to the myelin proteins only, thereby inhibiting the disease in mice. It is based on an earlier finding by Professor Miller that proteins coupled to dead blood cells can induce immune tolerance to these proteins. The method using dead cells, also inhibits multiple sclerosis and is undergoing early clinical trials in humans currently, but is extremely expensive and time-consuming to administer and very difficult o standardize. “This new nanoparticle approach, is much cheaper to produce and very easy to standardize”, said Professor King. “Furthermore, the nanoparticle we have used is made of poly-lactic co-glycolic acid (PLGA), currently used in many self-dissolving stitches in surgery, and breaks down naturally in the body. Importantly, it is already FDA-approved, which will enable clinical trials in humans sooner rather than later. The entire team is very excited about these results. We believe this breakthrough will open the door to the affordable future treatment of many autoimmune diseases.”
16TH OF OCTOBER 2012
Applications are now open for the following prizes administered through the Bosch Institute.
Bercovici Medal & Prize - Open to candidates for the degree of Doctor of Philosophy (best postgrad publication)
The Rebecca L Cooper Medal & Prize - Open to Postdoctoral Research Fellows (best postdoc publication)
For more information please go to here.
3RD OF SEPTEMBER 2012
Amanda Scopelliti, a PhD candidate, Pharmacology, has been awarded a John A Lamberton Research Scholarship. Established in 2004, these scholarships provide financial support for postgraduate scholars of exceptional ability who are working toward higher degrees at the University of Sydney in areas emanating from and inspired by the work of Dr John A Lamberton or in the area of science aimed at chemical understanding of brain function and malfunction.
As an undergraduate Amanda undertook a Bachelor of Science at the University of Sydney with majors in Biochemistry and Neuroscience, from which she graduated in 2010 with First Class Honours. Following the success of her Honours year, Amanda was awarded a University Postgraduate Award to support her post-graduate studies. She has continued research into her PhD in 2011, with a focus on investigating the molecular determinants of substrate and ion selectivity in glutamate and neutral amino acid transporters. Glutamate transporters are involved in multiple neurological disorders, while neutral amino acid transporters have implications in cancer growth. Amanda’s research aims to achieve a better understanding of how these transporters work by investigating the molecular mechanisms involved in their function. From this research, it may possible to develop ways to manipulate their function for therapeutic purposes.
29TH OF AUGUST 2012
Professor Robert Vandenberg and Associate Professor Renae Ryan discuss the background to their joint work on membrane transporters in the brain, which may impact treatment of neurological disorders. This article was featured in the September 2012 issue of International Innovation which is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the publication can be found at: http://www.researchmedia.eu.
Firstly, how do your research areas complement one another’s understanding of neuroscience?
We have worked together for a number of years and have a mutual interest in how membrane transporters work. Over the years we have developed our technical expertise; Renae did her PhD with Rob and then left the lab for three years to do postdoctoral work at Columbia University and NIH. During her postdoc, Renae learnt how to crystallise transporters and study purified membrane proteins. Meanwhile, Rob has continued his interest in electrophysiological and mutagenesis approaches to understand the structural basis for transporter function. We bounce ideas off each other virtually every day and our combination of approaches fit naturally together.
What has been the overarching focus of your latest research?
The main goal of our research is to understand how neurotransmitter transporters work at a molecular level. We focus on the transporters for the neurotransmitters glycine and glutamate which play an important role in cell to cell communication in the brain. Our ultimate goal is to develop novel therapeutics that target these transporters in disease states such as Alzheimer’s disease, schizophrenia and chronic pain.
Could you expand on your investigations into glutamate transporters?
Our work on glutamate transporters is at a more fundamental level where we are interested in understanding the mechanism of transport. This includes identifying the binding sites for substrate and coupled ions and also exploring the conformational changes that occur during the transport process as glutamate is shuttled across the cell membrane. The glutamate transporters are very interesting proteins in that they also have channel-like activity where they allow the movement of chloride across the cell membrane. Along with other groups, we have shown that these two components of transport can be independently manipulated and we have also identified part of the chloride permeation pathway through the transporter. We are continuing to work on mapping the chloride pathway through the transporter in order to better understand the interplay between the two functional states.
Why is the neurotransmitter glycine so critical in our understanding? How was the glycine transporter protein’s signifi cance originally discovered?
Glycine is the simplest of all amino acids and plays many roles in the body. In the CNS it is both an inhibitory and an excitatory neurotransmitter. In some classic studies in the 1960s using cat spinal cords, glycine was established as inhibitory neurotransmitter and it serves to dampen excitability of neurones. However, the inability to pharmacologically manipulate glycine concentrations in the spinal cord severely hampered study in this area for many years. The 1990s saw the cloning of various neurotransmitter transporter genes which has provided the tools to develop selective glycine transporter inhibitors. Two distinct glycine transporter genes were identifi ed and show quite different expression patterns in the CNS, which suggested that it should be possible to selectively manipulate glycine concentrations that correspond to the regions of the two transporter subtypes.
How do you ensure your results are delivered to the public in order to engage and inform? What is the most challenging aspect of effective dissemination?
Our lab works at the fundamental level and most of work is published in academic research journals. We see our role as providing basic information that the pharmaceutical industry can exploit in developing new therapeutic approaches and also for clinicians to better understand disease processes. The challenging aspect of communicating our work is to educate the public about how this research pipeline works. There is a great need for basic research, like ours, so that the pharmaceutical industry and clinicians can take the principles we identify to develop new therapeutics to treat debilitating disorders.
A team at the Bosch Institute in the University of Sydney is developing novel lipid based inhibitors which could have implications for disorders ranging from schizophrenia to Alzheimer’s disease.
The World Health Organisation has estimated that neurological disorders affect one in seven people worldwide, with colossal cost and disease burden. The impact of these diseases cannot be ignored, and a team based at The University of Sydney’s Bosch Institute has been seeking to better understand – and eventually treat – these conditions in their novel investigation into drug binding sites on glycine transporters. The hope is that they will be able to develop innovative, selective, lipid based inhibitors which may have therapeutic potential for the treatment of two major neurological disorders, schizophrenia and neuropathic pain. Work has already been completed on Glycine Transporter 1 (GlyT1) inhibitors, which is believed to help alleviate the negative symptoms of schizophrenia. Within the brain, NMDA receptors require glycine as co-agonists, and it was postulated that inhibition of GlyT1, a glycine transporter, would elevate glycine levels, causing a stimulation of NMDA receptors and alleviating schizophrenic symptoms, leading to a number of GlyT1 inhibitors undergoing clinical trials. The group’s work on GlyT2 is set to have a similar impact on the relief of chronic pain, although research is currently far less advanced.
Professor Robert Vandenberg and Associate Professor Renae Ryan lead an investigation to understanding how glutamate transporters work. Their research aims to address a number of major neurological diseases, all of which alter the body’s use of glutamate, since dysfunctions of glutamate transporters impact numerous metal health conditions. One of the 20 amino acids commonly found in proteins, glutamate also functions as a neurotransmitter and functions as part of learning, memory and motor abilities when it is correctly controlled. Ryan is aware of the impacts this research can have: “In Alzheimer’s disease and Motor
Neurone Disease, there is a reduced capacity to regulate glutamate levels, and it is thought that prolonged elevated glutamate levels lead to neuronal damage”. Since Alzheimer’s disease affects nearly 30 million people worldwide, this work comprises a major branch of research. Similarly, in the aftermath of a stroke, a failure in controlling glutamate concentrations commonly occurs with negative consequences for the central nervous system. In fact, glutamate disruption has been linked with most numerous high profile neurological disorders, including Huntington’s disease, Parkinson’s disease, epilepsy, depression, brain trauma, drug addiction, and alcoholism. The team’s work on glutamate transporters, is attempting to uncover the mechanisms by which the body controls glutamate levels. By doing this, Vandenberg and Ryan are opening up potential treatment avenues for these conditions, and a better understanding of the mechanisms behind neurological diseases.
A number of novel biochemical and molecular techniques have been deployed in order to paint a clearer picture of transporter structure and function, as well as delineating how they can be manipulated by endogenous and exogenous compounds. The range of techniques open to Vandenberg and Ryan is, in part, a function of the leading collaboration at the heart of the investigation. Ryan has contributed knowledge of recently developed techniques, meaning that they are now able to form crystals of transporter proteins, an essential stage in determining high-resolution structures, and also study the function of purifi ed proteins in liposomes; artifi cial lipid bilayer structures. Collaboration with biophysicist Dr Serdar Kuyucak has also led the team in interesting directions, utilising pioneering methods to simulate the structure and function of transporters. These advances have developed from the initial cloning of genes which encode the neurotransmitter transporters, which were then expressed on the cell surface of Xenopus laevis oocytes. Since the transport of both glutamate and glycine involves charged molecules moving across the membrane of the oocyte, electrophysiological techniques can be used in order to monitor the transport process. By combining these techniques, the Tuning transporters
A team at the Bosch Institute in the University of Sydney is developing novel lipid based inhibitors which could have implications for disorders ranging from schizophrenia to Alzheimer’s disease team hopes to make precise predictions about the transporter mechanisms, how drugs will interact with the proteins, and then provide tests within an idealised system.
This avenue of research may also have an impact on the treatment of chronic pain, which is widespread, though it is notoriously difficult to obtain objective statistics on its prevalence. Current estimations in most economically developed countries put the number of people who suffer from chronic pain at around one in five. Treatment options for individuals affected by the condition have a number of drawbacks, including escalating doses and addiction; consequently, pursuing alternative pharmacological approaches to pain relief is a worthwhile effort. Vandenberg and Ryan are confi dent that their work is leading in this direction: “Although there is considerably more work to be done, GlyT2 inhibitors show promise and may provide analgesia in conditions such as neuropathic pain an inflammatory pain”. N-arachidonyl-glycine (NAGly) is a GlyT2 inhibitor, and provides analgesia in rat models with these kinds of pain, and as a result, the project is identifying the molecular mechanism of NAGly’s action, hoping to identify an alternative class of analgesics. Whist this work is still in the early stages, progress to date has been promising. Whether GlyT2 inhibitors will have undesirable side effects remains to be seen, but the Vandenberg and Ryan are hopeful that their work will be useful.
Still currently at the laboratory stage, the investigation is building up the basic understanding of transporter functions in order to assist in their manipulation. Although early in the process, there is hope that the work will move to clinical trials at some point. The team are collaborating with Chris Vaughan, from Sydney’s North Shore Hospital, to test GlyT inhibitors as ameliorators for animal pain. If any of the compounds explored demonstrate therapeutic potential, they will begin the search for clinical collaborators. The partnerships of the joint team do not end there, since they are also working with a group from the Centenary Institute in Sydney. Here, they work with patients with amino acid metabolism disorders, characterising the transporter mutations which are responsible for their conditions. This group is also looking to fi nd blockers of amino acid transport into cancer cells, searching for a mechanism to starve these cells of nutrients and reduce their rate of growth. Vandenberg and Ryan’s team are helping in the investigation of mechanisms to inhibit these compounds, further broadening the outlook of their research.
Support of Sydney
The wide applicability of the work has been helped by the supportive research environment in which it has been conducted. For Vandenberg and Ryan this has been instrumental in their success: “The major asset of the Bosch Institute at the University of Sydney is the people who work here, resulting in a very dynamic research environment and an extremely collegiate atmosphere”. The pharmacology department has wide ranging expertise, from the cell biology of pain through psychopharmacology, protein structure and function to medical chemistry, providing both a stimulating environment. A dynamic postgraduate research programme also contributes to this research, providing a strong basis for the studies conducted within the university and demonstrating an investment in ongoing research potential. Facilitated by this context, Vandenberg and Ryan hope that they will be able to continue making progress, providing the understanding necessary to make breakthroughs in the treatment of neurological disorders.
Please click here to see more details.
12TH OF AUGUST 2012
Raising awareness for medical research - the Bosch Institute - fielding a team of 14, achieves a placing of 72 out of 536 teams.
Sunday 12th August saw a team from the Bosch Institute run in the annual City2Surf event; of the 14 runners who signed up for the race, 10 competed on the day, with illness affecting the team. Team members were spread throughout the race, from the red group, leading the pack up front, to the orange group at the back of the pack, and all completed the course.
The teams fastest runner was Marco Morsch, who ran the course in 66 minutes, followed closely by Thomas Szecnik with a time of 67 minutes. All Bosch Team team members performed fantastically, with the majority of them first-time runners. Despite the cold and blustery day, the team came 72nd out of 536 teams within the mixed open category, with nearly 80,000 runners all up, this is a wonderful result.
A big thanks to Angela O'Connor, Bosch Institute, for getting the team together, arranging weekly training and coordinating the 'finish' end of race picnic.
Angela thanked the Institute for their support and advised that she looks forward to entering another team in 2013 - to raise awareness for medical research and the Bosch Institute.
Congratulations again to all our runners in the team this year for their fantastic performance!
2ND OF AUGUST 2012
Vision scientists have discovered a new avenue for the treatment of vision loss, one of complications of Parkinson’s disease.
Gentle, non-invasive treatment with a soft infra-red light can potentially protect and heal the damage that occurs to the human retina in in Parkinson’s disease, says Professor Jonathan Stone from The Vision Centre and The University of Sydney.
“Near infra-red light (NIR) treatment has long been known to promote the healing of wounds in soft tissues such as skin. Our recent studies are showing that it can also protect the retina of the eye from toxins which attack its nerve cells,” Professor Stone says.
“We have been studying a mouse ‘model’ of Parkinson’s disease, in which such a toxin is used to create a Parkinson-like condition. The toxin targets brain cells which use a particular signalling molecule called dopamine, and the infrared light – in the right dose and with the right timing – blocks the toxic effect.”
The toxin also kills certain key retinal cells which use dopamine which are important in giving sharpness to the retina’s coding of visual images. However infrared light also protects these retinal cells and reduces the damage.
“This protection or rescue of neurones in the brain – and as we know now, in the retina – is better than the best established treatments for Parkinson’s disease,” Professor Stone says. “The challenge now is to translate these findings, made in mouse models, to human patients suffering from Parkinson’s disease.”
The research has also raised important new questions, he adds. “How, for example, does the infrared light create this protection? The answer seems to be that the radiation reverses damage to the cells’ machinery for the production of the energy it needs, from oxygen. With their energy production restored, damaged cells repair themselves, and resume function.
“Does the radiation work if given before the cell is damaged, or only after it is damaged? The rescue effect is there either way”, says Professor Stone. “We have much to learn about the mechanism and its timing, but these initial observations are encouraging.
“As to how soon it can be applied clinically, there are already dozens of clinical trial published, using infrared light for soft tissue wound healing and for pain relief. Small but good quality clinical trials have been reported for human vision, in age-related macular degeneration, and for stroke damage to the brain.
“Our new results suggest that infra-red radiation will be effective in Parkinson’s disease. Because the radiation is effective at low intensities, with no known toxicity, there are few barriers if any to trials in humans.
”Diseases like Parkinson’s are seriously debilitating; for the individual the need is immediate. There is every reason for trials to be carried out as soon as possible.”
As to the potential benefits for Parkinson’s patients, he says: “Principally, we anticipate there would be a preservation of acuity, the clarity with which we can see detail and contours in the visual world. The same treatment should be protective for the brain as well, preventing or slowing the otherwise relentless progress of the disease. As always, we will need rigorous trials, to know what can be achieved.”
Finally, he says, it is no surprise that the same treatment works for both the brain and the retina: “The retina of the eye is really part of the brain – the only part outside the skull. It has to be outside the skull, so it can function as an eye. In many ways the retina is the most accessible part of the brain, and many discoveries about the brain have begun in the retina.”
“Parkinson’s is a double-whammy disease,” says Professor Stone. “Our dream is turn back both the damage to the brain, and the damage to the retina. Increasingly, this seems possible.”
The study “Survival of Dopaminergic Amacrine Cells after Near-Infrared Light Treatment in MPTP-Treated Mice” by Cassandra Peoples, Victoria E. Shaw, Jonathan Stone, Glen Jeffery, Gary E. Baker and John Mitrofanis was published in ISRN Neurology. A copy of it is available at http://1.usa.gov/MxzpSQ.
1ST OF AUGUST 2012
The Neural Control and Autonomic Regulation (NCAR) section of the American Physiological Society has named Professor Roger Dampney as the 2013 Carl Ludwig Distinguished Lecturer. Roger will present this lecture at the Meeting of the American Physiological Society in April 2013 in Boston.
The Neural Control and Autonomic Regulation (NCAR) section of the American Physiological Society has named Professor Roger Dampney as the 2013 Carl Ludwig Distinguished Lecturer. Roger will present this lecture at the Meeting of the American Physiological Society in April 2013 in Boston. The Lecturer is selected by members of the NCAR Section as a representative of the best within the discipline. Roger is the second Australian to be awarded this honour, the previous recipient being Professor Murray Esler of the Baker Heart Research Institute.
20TH OF JULY 2012
Congratulations to Myriam Abboud, who is currently undertaking a PhD on vitamin D with Rebecca Mason and David Fraser, for the award of a special invitation to attend the 1st Asia-Europe Students’ Forum at The University of Groningen. This Forum engages graduates who have become professionals or entrepreneurs, to perform a reality check on working life after graduation and the efficacy of skills learnt at University. Myriam is an Accredited Practicing Dietitian, who established All About Nutrition private practices in 2009. These nutrition clinics are based in medical centres in various areas in the Sydney metropolitan area and offer dietetic consultancy to individuals and corporations. At the Forum in Groningen, Myriam will take part in discussions and workshops about Universities and Business programs for a Sustainable Future.
30TH OF APRIL 2012
Dr. Rachel Codd has been awarded a 2012 grant from Parkinson’s NSW to study new compounds she has developed that may have potential to mobilise iron in the brain. Elevated iron in the substantia nigra region of the brain has been implicated in the pathobiology of Parkinson’s disease. The ability to mobilise brain iron will allow a better understanding of iron-induced toxicity and will inform new therapeutic approaches. Dr. Codd and her team will use the funds to evaluate the ability of the compounds to modulate iron-induced toxicities in in vitro models of Parkinson’s disease. The research was featured on Channel 10 News earlier this year. Click for the video.
20TH OF APRIL 2012
Researchers in the University of Sydney’s Bosch Institute are reporting novel and powerful ways of stopping the growth and spread of cancers. The Iron Metabolism and Chelation Program headed by Professor Des R. Richardson has shown, moreover, that the new anti-cancer agents – called iron chelators – can control a range of cancers, yet can do so with minimal side effects.
Professor Richardson: “We are focusing on iron chelators because they attack a fundamental characteristic of cancer cells, yet leave normal cells alone. We believe they have the potential to be ‘next generation’ drugs, for a range of cancers, including highly aggressive pancreatic cancer”.
Prof. Richardson’s group has recently published two key articles in the Journal of Biological Chemistry and Antioxidants and Redox Signaling which describe the molecular mechanisms involved in the anti-cancer activity of these novel agents.
This work was led by post-doctoral researcher and NHMRC Early Career Fellow, Dr. Zaklina Kovacevic, and formed part of her prize-winning PhD thesis. Her work demonstrated that these novel iron chelating agents increase the levels of a molecule (NRDG1) which inhibits the spread of cancer.
Prof. Richardson is optimistic that these recent findings will lead to the development of iron chelators as an effective new strategy for cancer treatment:-
“Currently, I am having advanced discussions on a licensing deal with the American Company, Pecan Biotherapeutics Inc. (Dallas, Texas), for the development of these chelators to the stage of clinical trials.. Translation to clinical trials is a difficult step; it has been greatly helped by the Bosch Institute’s Translational Grants program, and by an NHMRC Development Grant.”
Dr. Kovacevic (pictured) believes that “The entry of these novel agents into clinical trials will present a significant step forward in the fight against cancer and provide cancer sufferers new hope for a better outcome.”
The Executive Director of the Bosch Institute, Professor Jonathan Stone: “For anyone who has been through, or cared for a cancer sufferer through, the purgatory of chemotherapy, the prospect of anti-cancer drugs which are broadly effective, yet minimal in side effects is immensely welcome.”
Harbour Cruise to Welcome New Young Investigators
01ST OF APRIL 2012
Every year a Harbour Cruise is organised by the Bosch Young Investigators. This serves to welcome new members, is an opportunity for people from different disciplines to socialise, and is always a fun night!
The Bosch cruise 2012 was a huge success with more than 130 students attending dressed as their favourite movie character. The night was full of eye catching costumes and lively conversations. Cruising around Sydney harbour provided pleasurable scenic views to soak up the night with. It was an amazing cruise which allowed students to shed the stresses of life and dance the night away. Read more...
06TH OF MARCH 2012
A record attendance for the 2012 SMS/Bosch New Researchers Program this year with 80 students (mostly Honours students) enjoying the two day program (6th & 7th March). Students reported that the program was very helpful and informative. Topics covered this year included - Writing a Thesis, Giving a Seminar, Occupational Health and Safety, Intellectual Property, Ethics, Digital Imaging/Powerpoint, Endnote, Experimental Design and Bosch Facilities Overview.
Please click to see the program (PDF 10KB).
02ND OF MARCH 2012
Tuesday the 21st of February saw 26 members of the Bosch Institute- comprising of Masters, PhD students and Postdocs together with a handful of Academics, depart the University to embark upon the 3 day Bosch Young Investigators Retreat at the Kioloa Coastal Campus. The meeting was an enormous success - please see the participants feedback and student and academic report by clicking the link below.Read more...
01ST OF FEBRUARY 2012
Top Left –Chan-Ling Lab members whose work is displayed. Seated – Prof. Tailoi Chan-Ling. Standing (L-R) – Dr. Michael Lovelace, Steven Eamegdool, Dr. Hussein Mansour.
Bottom Left – Cultured human neural precursor cells, expressing multiple cytoskeletal markers. Proliferating cells are labelled with pink nuclei (Steven Eamegdool).
Centre Top – Section through a neurosphere which wholly expresses GFAP a marker of astrocytes and their precursors (Dr. Michael W Weible).
Centre Bottom – Migrating neural precursor cells from an adherent neurosphere. Co-expression of markers of undifferentiated neural precursor cells is indicated by yellow labelling, while small numbers of differentiated cells were identified in the fringe region of the monolayer (Dr. Michael Lovelace).
Top right – Network of GFAP+ retinal astrocytes (red) surrounding blood vessels (blue); green labelling is astrocyte somas (s100beta+) (Dr. Hussein Mansour)
Bottom right – Network of cultured dorsal root ganglion neurons, satellite cells and Schwann cells, labelled with di-8-ANEPPS (Dr. Michael Lovelace in collaboration with Laita Bokhari, Dr. Roberta Chow and Prof. Patricia Armati, Neuroinflammation Group, Brain and Mind Research Institute).
Application of the latest advanced imaging techniques in the pursuit of key basic biological questions is a long tradition in the laboratory of Prof. Tailoi Chan-Ling, begun in the late 1980’s. Recognition of the high standards achieved has come via a string of accolades awarded to the young investigators in her laboratory. Her laboratory’s data has graced the covers of 4 international journals of high impact, the Bosch Institute website, the halls of museums and international research institutes, and now the NHMRC web site. Together, they demonstrate the beauty that can be captured in biological structures, whilst gaining novel insights on biological processes. These achievements would not be possible without the outstanding support of Dr. Louise Cole (Bosch Institute Advanced Microscopy Facility Officer) and access to the latest microscope technology provided by the Bosch Institute.
In 2007, postdoctoral fellow Dr. Michael Weible was awarded 1st prize in the Bosch Institute Advanced Microscopy Facility Micrograph of the Year competition for his image of a sectioned neurosphere. Neurospheres are a spherical cluster of cells of the developing nervous system, grown in vitro and used to investigate the biological and physiological processes governing the commitment of multipotent neural cells to a specific lineage e.g. neurons. In 2009, PhD candidate Hussein Mansour was awarded 2nd prize in the same competition for his image depicting multiple-marker immunohistochemistry of a retinal whole mount (see figure for all prize-winning images). His work then led to the development of a method for 6-marker immunostaining, a novel technical breakthrough not applied previously to the study of the retina. Hussein has also won international micrograph competitions including first prize in the 2005 Olympus Bioscapes (featured in the prestigious scientific journal “Nature”, Dec. 2005, volume 438, pp. 1063) and a 2nd prize in the 2010 Eurovision competition with his stunning confocal images. Most recently, fellow PhD candidate Steven Eamegdool won first prize in the 2011 Bosch Institute micrograph competition, and postdoctoral fellow Dr. Michael Lovelace received a highly commended award in both the prestigious 2011 NHMRC Science to Art Award and the Bosch Institute Molecular Probes image prize, and he was also runner-up in the 2010 competition for his spectacular images of migrating cells of the developing nervous system.
An overall unifying theme to the lab’s research has been the study of the retina as a model of the brain in order to further our understanding of the developmental biology of the glial cells and vasculature of the central nervous system. The laboratory has also made a major contribution to the understanding of the cellular mechanisms by which new vessels are formed in the retina and choroid during normal development, and in various disease processes.
We have also studied the glial, vascular & immune response in various diseases that involves the blood vessels, including retinopathy of prematurity (ROP), cerebral malaria, and inflammatory demyelinating disorders such as multiple sclerosis (MS), physiological aging and more recently, diabetes. Other current projects in the laboratory aim to investigate the potential application of neural stem/precursor cells in animal models of stroke. Further studies are underway using calcium imaging to understand the physiological signaling of these cells. Recent outcomes of this work include the discovery of a family of receptors (purinergic receptors) in both human neural precursor cells and early committed neurons. Activation of these receptors can induce changes in proliferation, and differentiation, which are critical features of the developing nervous system, and can be modelled in vitro. This work has therefore given the lab exciting new avenues for future research, and the lab would welcome enquiries from prospective Honours and PhD students.