Honours Projects - 2008

The projects listed below are available to "Honours" candidates in 2008. These one-year research programs are available in a number of programs which can accommodate a wide range of students. The current year Honours home page gives information on the current program and students.
Prof. D.G. Allen is responsible for the administration of these programs, and should be contacted for general information (Room N421, Anderson Stuart Building, Tel: +61 2 9351 4602) (davida@physiol.usyd.edu.au). Potential supervisors should be contacted to discuss specific opportunities.

For quick reference, here are links to all the Laboratories listed below:

* Audiovisual Research Laboratory - Dr David Alais
* Laboratory of Motor and Sensory Systems - Dr Haydn Allbutt
* Muscle Cell Function Laboratory - Professor D.G. Allen
* Andrology Research Group - Dr Stepehn Assinder
* Neurobiology Laboratory - Professor M.R. Bennett
* Auditory Neuroscience Laboratory - Associate Professor S. Carlile
* Epithelial Transport Laboratory - Professor D.I. Cook
* Comparative Auditory Neuroscience Laboratory - Dr. Christine Koeppl
* Cardiovascular Neuroscience Laboratory - Professor R.A.L. Dampney
* Laboratory of Developmental Neurobiology - Dr C. Leamey
* Bone & Skin Cell Laboratory - Professor R.S. Mason
* Environmental Control of Physiology Laboratory - Dr Bronwyn McAllan
* Basic & Clinical Genomics Laboratory - Professor B.J. Morris
* Embryonic Stem Cell Laboratory - Dr Michael Morris
* Human Reproduction Unit, RNSH - Associate Professor C. O'Neill
* Molecular Neuroscience Laboratory - Dr W.D. Phillips
* Vision Laboratory - Dr D. Protti
* Systems Neuroscience Laboratory - Dr Atomu Sawatari
* Laboratory of Vision & Cognition - Dr Sam Solomon
* External Honours Projects


AUDIOVISUAL RESEARCH LABORATORY, Anderson Stuart Bldg, Room N438, Telephone: +61 2 9351 7615

Dr David ALAIS directs a cross-modal research group which conducts visual and auditory research and has a particular interest in understanding how both sources of sensory information are combined in the brain. The primary approach is through human psychophysical experiments which measure aspects of an observer's perception of sounds, images or combinations of both. From these measurements, inferences are drawn as to how various neurophysiological mechanisms give rise to perception.

The laboratory welcomes projects focusing on purely visual or auditory aspects of perception, as well as those combining both modalities. A broad variety of visual stimuli may be custom programmed in the laboratory and our close collaboration with Assoc. Professor Carlile's Auditory Neuroscience Laboratory means that sophisticated auditory stimuli are also available. Sounds may be presented in the free field using a large anechoic chamber or via earphones using the laboratory's sophisticated virtual auditory space (VAS) technology.

Some particular interests in the laboratory which may suit Honours projects include:

  1. How the brain resolves visual conflict between the eyes (binocular rivalry)
  2. How visual and auditory information is weighted in cross-modal integration.
  3. How rapid head movements affect auditory perception.
  4. How the monaural and binaural cues to sound location are combined by nervous system.
  5. How movement and temporal modulation is encoded by the visual system.

Direct enquiries can be made by email to: Dr David Alais - alaisd@physiol.usyd.edu.au


LABORATORY OF MOTOR AND SENSORY SYSTEMS. Anderson Stuart Bldg, Room N243, Telephone: +61 2 9351 2515

Dr Haydn Allbuttís laboratory is interested in working out how the body moves and senses its environment, using interesting neurological conditions as the basis for investigation into these pathways.

Project Title: Development of a new model of Parkinsonís Disease
Supervisors: Dr Haydn Allbutt
Project Description:
One of the primary focuses of the laboratory is to investigate possible causes of Parkinsonís Disease, a debilitating condition which affects 1% of people over the age of 65. Despite being described over 190 years ago, the cause of the condition is still not known. This project aims to evaluate a possible cause of Parkinsonís Disease by investigating the symptoms and neural changes that occur as a result of insults to specific cell types in the CNS. In addition, the project will include an investigation into a possible blood test for the beginning stages of Parkinsonís Disease, which if successful will provide an earlier diagnostic blood test than anything currently existing. ...more

Project Title: Investigation into olfaction as an early symptom of Parkinsonís Disease
Supervisors: Dr Haydn Allbutt
Project Description:
This project is an exciting project that has two stages. The first stage will be to work on developing a new test of olfaction, the hole-board olfactory test, using normal rats. The reason for this is that along with the characteristic shaking associated with Parkinsonís Disease one of the most prevalent symptoms is loss of smell, with 80-100% of patients being affected. It is also thought that loss of smell may present much earlier than motor deficits, and thus may be an early indicator of neurodegeneration, prior to other symptoms. Being able to detect Parkinsonís Disease early would be of great benefit as it would allow the use of neuroprotective therapies in order to halt the progression of the disease, before a debilitating level of loss has occured.

The second stage of this project is that once the olfactory test has been developed it will be used to examine olfaction in two animal models of Parkinsonís Disease, the standard 6-OHDA model and also a new model being developed in this lab. This project will combine the excitement of developing and validating new methods never before used in science with new research into the second most common neurodegenerative disease in our society. The results obtained will potentially provide important information into one of the major symptoms of Parkinsonís Disease and also investigate the value of this symptom in the early diagnosis of the disease. ...more

For Direct enquiries email Dr Haydn Allbutt - hall@physiol.usyd.edu.au or phone 9351 2515


MUSCLE CELL FUNCTION LABORATORY, Anderson Stuart Bldg, Room N421 Telephone: +61 2 9351 4602

Professor D.G. ALLEN

The Muscle Cell Function laboratory is concerned with the regulation of calcium and other ions in cardiac and skeletal muscle cells.

Project Title: Mechanisms of muscle damage in muscular dystrophy
Supervisors: David Allen & Nick Whitehead
Project Description:
Duchenne muscular dystrophy is severe degenerative disease of muscle which causes death in affected boys by the age of 20. Dystrophic muscles are more sensitive to stretch-induced muscle damage and this may be part of the damage pathway. We have recently shown that blockers of stretch-activated channels prevent Na and Ca entry into muscles following stretch-induced damage and also reduce some of the muscle damage. In this project muscles will be removed from mdx mice (an animal model of muscular dystrophy) and the ability of drugs to reduced muscle damage will be tested.

Project Title: How the pacemaker controls the heart rate
Supervisors: David Allen & Yue-kun Ju
Project Description The pacemaker region in the mouse heart contains a recently discovered store operated channel whose role in the pacemaker activity is under investigation. The project involves isolating intact sino-atrial nodes of mice and investigating function with electrophysiology, fluorescent calcium indicators and immunohistochemistry.

Direct enquiries can be made by email to: Professor David Allen - davida@physiol.usyd.edu.au


Andrology Research Group , Anderson Stuart Bldg, Room E216 Telephone: +61 2 9351 2514

Dr Stephen Assinder

Prostate disease is very common in the ageing male. Prostate cancer is the second most frequent cause of cancer-related death and benign tumours affect approximately 50% of men over 60 years of age.

Project Title: Prostate Cancer and benign prostatic hyperplasia
Supervisor: Stephen Assinder
Project Description:
Our research is focused on:

  1. Understanding how the loss of structural proteins involved in organization of the cell cytoskeleton contribute to the development of prostate cancer phenotypes
  2. Hormone regulation of prostate cell proliferation. In particular we are interested in how oxytocin, a hormone usually associated with females, regulates enzymes that are essential to growth of the prostate and to determine if different cell signal pathways are involved.
  3. The roles of Ca2+ activated K+ channels in the abnormal proliferation of prostate stromal cells. Several studies have described and Ca2+-inactivated K+ channels in regulation of cell proliferation of prostatic epithelial cancer cell lines. There are scant reports of such channels in human prostate stromal cells (PrSC) and no knowledge of the estrogen regulation of these cells and effects on cell proliferation. This work is in collaboration with Dr Kirk Hamilton, University of Otago.

Projects are available in these areas of interest. They will employ many techniques including cell culture, proliferation assays, RT-PCR, real time PCR, siRNA knock downs, Western blot, Immunohistochemistry, thin layer chromatography and radioimmunoassay.

Direct enquiries can be made by email to: Dr Stephen Assinder - stephena@physiol.usyd.edu.au


NEUROBIOLGY LABORATORY, Anderson Stuart Bldg, Room N101 Telephone: +61 2 9351 2034

Professor M.R. BENNETT

The Neurobiology laboratory is now concentrating on signal transduction in glial cells, communication between neurons and glial cells, and their applications to neuronal disorders both in central and peripheral nervous systems. Recent studies demonstrate glial cells are active partners in processing information and synaptic integration. However, it is not clear what code signals that glial cells receive from neurons are and how glial cells affect neuronal activity. Furthermore, it is not know if this communication is in normal order, and if not, what changes are in neuronal disorders such as Parkinson’s disease.
Recent studies of neuropathic pain states, such as extraterritorial and mirror image pain, have led to new insights concerning a crucial role of aspinal cord astrocytes in creation and maintenance of these pathological painstates. P articularly, in dorsal horn, astrocytes were always dramatically activated in response to diverse axonal lesions that create exaggerated pain. However, it is not know how astrocytes communicate each other and what messengers mediate these communications.

To address the above issues, we examine communications between neuronsand glial cells, and signal transduction among the glial cells in both central nervous system and peripheral nervous system. Multiple techniques are tobe used in these studies, which include tissue culture, brain (spinal cord)slice, calcium imagine, electrophysiology, luciferin-luciferase (ATP) assay,and imunohistochemistry.

Projects:

PAIN: CELLULAR AND MOLECULAR GLIAL MECHANISMS

Project Title: The cellular origins of neuropathic pain: glial cells, macrophages and cytokines
Supervisor: Prof Max Bennett
Project Description:
The fundamental problem in ameliorating neuropathic pain is to block the spontaneous action potential firing, which originates primarily from nociceptor nerve endings in the neuroma formed at the site of nerve lesion. Nociceptors have specific classes of Na+ channels which are modified following a lesion, with tetrodotoxin-sensitive channels up-regulated and insensitive ones down-regulated. The question arises as to what are the mechanisms at the lesion site that engage this transformation in Na+ channel types. There is a proliferation of glial cells (Schwann cells) and macrophages at the neuroma, which are known to release certain species of cytokines, growth factors and transmitter substances. These must engage a retrograde transport system in the injured axons, so as to signal to the nociceptor neuron's nucleus the changes in Na+ channel expression with a concomitant orthograde redistribution of these channels to the site of the neuroma. The capacity to block specific and unique components of these processes lies at the heart of achieving specific oral analgesics without gross side-effects. Of special interest in this regard is the action of lidocaine and of P2x7 receptor antagonists. This project, which is at present the subject of experimentation in our laboratory, involves a comprehensive consideration of these pathways and mechanisms.

References
Wall & Malzack (2005) Text Book of Pain, 5th edn, Chapter 58.
I. Nagg & C. Woolf (1996) Pain 64(1): 59-70.
M. Araujo, C. Sinnott et al., (2003) Pain 103(1-2): 21-29.
R. Amir, C. Argoff et al., (2006) Journal of Pain 7 (5 Suppl, 3): S1-S29.
G. Liu, E. Werry & M.R. Bennett (2006) Europ J Neurosci 21(1): 151-160.
G. Liu &M.R. Bennett (2003) NeuroReport 14(16): 2078-2083.

Project Title: The cellular origins of migraine pain: astrocyte spreading depression>
Supervisor: Prof Max Bennett
Project Description:
Headaches in migraine are thought to be associated with a dilation of cranial blood vessels, particularly those in the dura mater,and an accompanying localized sterile inflammatory response. In many cases the headache phase of migraine is preceded by a condition called aura, in which there is a disturbance of vision, consisting of bright spots and dazzling zigzag lines. This aura is associates with a spreading depression of electrical activity in the cortex. This depression of electrical activity involves a considerable increase in extracellular potassium and a concomitant decrease in extracellular sodium, chloride and calcium. Astrocytes are most likely to be the cell responsible for spreading depression. Calcium waves are propagated by astrocytes, whereas sodium waves (the action potential) are propagated by neurons. Synaptic transmission between astrocytes is mediated by the substance ATP, so that blocking this transmission should block or slow spreading depression. In order to do this, it is first required to identify the mechanism of ATP release and the receptors on which this nucleotide acts.
This project involves an analysis of the mechanism of the spreading depression responsible for both the aura and headache phases of migraine.

References
U. Reuter, M. Sanchez del Rio & M. Moskowitz (2000) Functional Neurology 15: Suppl. 3, 9-18.
L. Edvinsson (2001) Pharmacology and Toxicology 89(2); 66-73.
E. Hamel (1999) Canadian Journal of Clinical Pharmacology 6: Suppl. A., 9A-14A
M.R. Bennett, L. Farnell & W.G. Gibson (2005) Biophysical Journal 89(4); 2235-2250.
M.R.Bennett, V.Buljan, L.Farnell & W.G.Gibson (2006) Biophysical Journal (EPub)

Project Title: The cellular origins of central pain sensitisation I: the astrocyte - microglia network
Supervisor: Prof Max Bennett
Project Description:
The spontaneous action potential firing in nociceptor neurons generated at the site of a neuroma after a lesion causes neuropathic pain. However, after the lesion has healed on-going pain is often still experienced. There is evidence that an astrocyte - microglia cell network in the dorsal horn, at the site of nociceptor synapses, could mediate this process of sensitisation. Nociceptor nerve terminals, firing spontaneous bursts, release both glutamate and substance P which we have shown trigger the release of large amounts of ATP from astrocytes. In addition, microglia migrate to the site of such terminals, where they are in turn triggered to release ATP in response to glutamate release from the terminals. The very large ATP concentrations that ensue are such as to be able to activate P2x7 receptor-forming pores in the microglia, leading to the unregulated release of ATP and cytokines. This ATP/cytokine soup can then activate P2x receptors on the nociceptor terminals to greatly enhance the release of glutamate and ATP under even mild impulse traffic. The resulting positive feedback network ensures an increase in nociceptor transmission in the pain pathway that becomes independent of any elevated action potential firing in the terminals. The experimental and theoretical aspects of this pain sensitisation will be examined in this project.

References
M. Tsuda, K, Inoue,& M. Slater (2005) Trends in Neurosciences 28(2): 101-107.
A. Abdipranoto, G. Liu, E. Werry & M.R. Bennett (2003) NeuroReport 14(17): 2177-2181.
G. Liu, A. Kalous, E. Werry & M.R. Bennett (2006) Molecular Pharmacology (Epub).
E. Werry, G. Liu & M.R. Bennett (2006) Journal of Neurochemistry (Epub).

Project Title:The cellular origins of central pain sensitisation II: astrocytes, microglia and cytokines
Supervisor: Prof Max Bennett
Project Description:
Cytokines can have a powerful effect onboth transmitter release as well as on the distribution and density of transmitter receptors at synapses. For example, TNFa up-regulates AMPA receptors at glutamatergic synapses and ILib depresses transmitter release. Microglia at synapses are a principal source of both TNFa and ILib and glutamate greatly enhances the release of ILib from these glial cells. In project P3 above, we discussed the role of the astrocyte - microglia network in enhancing glutamate release from nociceptor terminals and of ATP accumulation at the synapses formed by these terminals. Given that microglia migrate to sources of high ATP, these cells can release TNFa in the glutamate -ATP rich environment. This cytokine enhances nociceptor transmission through up-regulating AMPA receptors, greatly increasing the transmission in the pain pathway. The mechanisms involved in the release of both pro-inflammatory and anti-inflammatory cytokines and their actions on nociceptor transmission will be studied in this project with the aim of identifying the appropriate sites of blockade to relieve the sensitising effects of cytokines in pain transmission.

References
D. Stellwagen & R. Malenka (2006) Nature 440(2082): 1054-1059.
F. Bianco, N. Solari et al. (2005) Journal of Immunology 174(11): 7268-7277.
D, Taylor et al. (2005) Journal of Neuroscience 25(11): 2952-2964.

Project Title: Pain representation in the brain: the astrocytic model for fMRI and the interpretation of images
Supervisor: Prof Max Bennett
Project Description:
Pain of superficial (cutaneous) origin is sharp and restricted, whereas pain of deep origin (muscle and viscera) is dull and diffuse. Using functional magnetic resonance (fMRI), major differences in the regions of the brain 'activated' in these different conditions have been noted by L. Henderson and his colleagues. These include regions associated with the emotions (perigenual cingulate cortex), with stimulus localization and intensity (somatosensory cortex) and motor control (motor cortex and cingulate motor area). However, the identification of regions as 'activated' depends on what fMRI is measuring, which is changes in the blood oxygen level development (BOLD). It is now known that changes in blood flow at the level of capillaries and arterioles is under the control of the endfeet of astrocytes whose processes enfold of the order of 10,000 synapses. Adenosine, nitric oxide and epoxyeicosatrenoic acids (EETs) are the substances released at the interface between astrocyte endfeet and the endothelial cells of blood vessels. These substances have powerful relaxing effects on the smooth muscle of blood vessels, leading to vasodilation and an increase in blood flow.

            The question examined in this project is:- what is the mechanism by which activity at synapses is conveyed to blood vessels through astrocytes, and to what extent the resultant BOLD signal changes can be said to reflect 'activated' brain regions? Without determination of this mechanism and the factors which perturb it, use of fMRI to investigate pain pathways in the brain must be carried out with some caution.

References
L. Henderson et al., (2006) Pain 120: 286-296.
A. Arthurs & S. Boniface (2002) Trends in Neuroscience 25: 27-31.
A. Volterra & J. Meldoles (2005) Nature Reviews Neuroscience 6: 626- .
C. Pepplatt & D. Attwell (2004) Nature 431: 137- .
R. Kochler et al., (2006) Journal of Applied Physiology 100: 302-317.

Direct enquiries can be made by email to: Professore Max Bennett - maxb@physiol.usyd.edu.au


AUDITORY NEUROSCIENCE LABORATORY, Anderson Stuart Bldg, Room N438, Telephone: +61 2 9351 3205

Associate Professor S. CARLILE directs a multi-disciplinary research group aimed at understanding the mechanisms by which the auditory system encodes sound direction and the perception of sound localisation. Sounds are generated in the free field and in so-called virtual auditory space (VAS). Research projects involve acoustics, neural coding, behavioural/psychophysical studies, computer simulations and digital signal processing. A major facility of the laboratory is a large anechoic chamber, equipped with one of the world's most advanced moving speaker assemblies. It is based on a high speed robotic arm rotating about a central axis, and designed to deliver sound signals positioned precisely in two-dimensional space.

Projects:

  1. Human psychophysical studies examining the role of spectral cues produced by the outer ear and head in generating our percept of external auditory space, and the localisation and streaming of auditory objects within that space. In this approach bio-acoustical measurements of the filtering of the outer ear are used to generate and manipulate sounds in virtual space. Here, digital signal processing is combined with classical auditory psychophysics to study the perception of stationary and moving sound sources.
  2. Neural and bioacoustical studies of the mammalian auditory system (guinea pig and ferret) are aimed at determining how the monaural and binaural spectral cues to a sounds location are encoded by the nervous system. Neurophysiological techniques involve conventional microelectrode recordings (single and multi-unit) from the midbrain and the analysis of neural responses to sound stimuli presented in the free-field and in VAS. The analysis of unit data includes newly developed spike-sorting and correlation procedures to improve da ta recovery, underlying a strong emphasis on digital processing and analytical techniques in the laboratory.

Direct enquiries can be made by email to: Associate Professor Simon Carlile - simonc@physiol.usyd.edu.au


EPITHELIAL TRANSPORT LABORATORY, Medical Foundation Building, Room 230, 92-94 Parramatta Rd Camperdown, Telephone: +61 2 9036 3314

Professor D.I. COOK

Project Title: Use of replication-deficient adenoviruses and retroviruses to investigate control of epithelial sodium channels in epithelia.
Supervisor: Prof David Cook
Project Description:
Use of replication-deficient adenoviruses and retroviruses to investigate control of epithelial sodium channels in epithelia.
There are several different aspects of this project, each of whichwould be suitable for an honours project. One aspect will be to examineto mechanism by which pathogens and particularly viruses regulatesodium channel activity. Another is to investigate the role of the sgkkinase in regulating sodium channel activity. The third is to examine themechanisms by which extracellular nucleotides such as ATP regulate sodiumchannel activity. Each of these projects combines molecular biology withelectrical measurements of sodium transport across epithelia.

Project Title: Identification of novel regulators of sodium channels.
Supervisor: Prof David Cook
Project Description:>
This project will use the yeast 2-hybrid technique to identify novel proteins regulating sodium channel activity.

Project Title: Use of replication-deficient adenoviruses to investigate regulation of cytosolic Calcium.
This project combine combine molecular biological and fura-2 methods to investigate the mechanisms by which agonists such as acetylcholine and ATP regulate the rate of Calcium trasnport out of cells.

Project Title: Characterisation of ClC family Chloride channels in salivary and other epithelia.
This project will use patch-clamp methods in cultured epithelia tocharacterise the chloride channels found in their membranes and to investigatethe mechanisms by which their activity is controlled.

Project Title: Investigation of the role of sodium-bicarbonate cotransport in early embryonic development.
This project will be jointly supervised by with Margot Day. It will use RT-PCR, western blotting and cytosolic pH measurements with the pH sensitive dye BCECF and will determine which isoforms of the sodium-bicarbonate cotransporter are present in pre-implantation mouse embryos and whether they play a role in regulation of cytosolic pH.

Direct enquiries can be made my email to: Professor David Cook - davidc@physiol.usyd.edu.au


CARDIOVASCULAR NEUROSCIENCE LABORATORY, Anderson Stuart Bldg, Room N640, Telephone: +61 2 9351 4603

Professor R.A.L. DAMPNEY's

The general theme of research in Cardiovascular Neuroscience lab is the control of blood pressure and sympathetic nerve activity by the brain (especially brain stem and hypothalamus) both under normal conditions and in abnormal conditions such as high blood pressure (hypertension). The laboratory uses a wide range of techniques and experimental approaches, including electrophysiology, immunohistochemistry, and more recently gene transfer methods.

Project Title: Hypothalamic Control of Caridovascular Function
Supervisor: Prof Roger Dampney
Project Title:

  1. The role of serotonin receptors (particularly of the 5-HT1a sub-type) in the brain in regulating increases in blood pressure, sympathetic activity and heart rate associated with stress. [Recent discoveries from our laboratory as well as others have demonstrated a highly specific and potent role of brain 5-HT1a receptors in these responses].
  2. The mechanisms by which higher brain regions increase sympathetic vasomotor activity, heart rate and respiratory activity during exercise. In particular, we wish to determine whether there are ďcommand neuronsĒ in the hypothalamus or other higher brain regions that have collateral outputs to both cardiovascular and respiratory neurons within the brain stem.
  3. The identification of neurons within the hypothalamus or other higher brain regions that are activated during alerting responses and which control the cardiovascular responses associated with thus behaviour.
  4. Role of angiotensin II (AngII) receptors in the brain in the regulation of sympathetic activity and blood pressure. We are particularly interested in determining whether alteration of the expression of AngII receptors (by means of gene transfer technology) in key cardiovascular nuclei will lead to sustained changes in blood pressure and heart rate. [AngII receptors in the brain are believed to have a crucial role in the maintenance of increased sympathetic activity in certain types of hypertension and heart failure].

Direct enquiries can be made by email to: Professor Roger Dampney - rogerd@physiol.usyd.edu.au


COMPARATIVE AUDITORY NEUROSCIENCE LABORATORY Anderson Stuart Bldg, Room N413, Telephone: +61 2 9351 5037

Dr Christine Koeppl

Our research aims to understand how the sensory and nervous systems of animals work and how they evolved within the context of their environment. What is the system capable of and how did it arrive there? How do different evolutionary solutions to the same problem compare and what can we learn from this with respect to human functions, both normal and diseased?

Available Honours Projects:

Project Title: The physical cues for sound localisation in the chicken
Supervisors: Dr Christine Koeppl
Project description:
The localization of sound is a computational problem that has to be solved by the central auditory pathways in the brain because the auditory receptor organ, the cochlea, contains no map-like representation of stimulus location. Animals and humans use slight differences in the timing and intensity of the auditory input to both ears to localize sound: When sound comes from one side of the body, it reaches one ear before the other and it is louder in that ear. The arising differences, however, are highly dependent on head size and shape. As part of our ongoing study of sound localization in birds, it is important to know exactly what interaural time differences are experienced by chickens. In collaboration with Dr. Carlile’s lab, the project will use electrophysiological and signal-processing techniques to map out this aspect of the chicken’s auditory world.

Project Title: Evolution of the cochlear efferent system
Supervisors: Dr Christine Koeppl
Project description:
An important part of the peripheral auditory system is the feedback control returning from the brain to the sensory cells of the cochlea, termed the efferent system. The efferent system in mammals (and humans) is complex and its functions are only partly known. Our approach is to study the different and mostly simpler forms of the efferent system in a variety of other vertebrate animals. This will enable us to separate its common, basic properties from more specialised functions added later in evolution. You could do an Honours Project tracing the efferent neural connections between the brainstem and the inner ear in selected species, using neuroanatomical labelling techniques. This will be combined with transmitter immunocytochemistry to test for subgroups of efferent neurones.

Project Title: The basis of fast temporal processing in the cochlea of the barn owl
Supervisors: Dr Christine Koeppl
Project description:
The barn owl is a well-established model for the fast temporal processing used in measuring interaural time differences for localizing sound sources in space. The owl serves as an example for the extreme performance of a basic mechanism that is used by many animals, including humans. The basis for its extreme performance is found at the level of the inner ear. We have shown that the afferent nerve fibres leaving the owl’s cochlea for the brainstem code the temporal occurrence of a stimulus with a precision of up to 20 microseconds. Although well documented, it is still unknown how that kind of precision is achieved. In this project we will investigate the ultrastructure of the very special synapses, so-called ribbon synapses, between the sensory hair cells and the afferent neurones, using transmission electron microscopy.

Direct inquiries can be made by email to: Dr Christine Koeppl - ckoeppl@physiol.usyd.edu.au


LABORATORY OF DEVELOPMENTAL NEUROBIOLOGY, Anderson Stuart Bldg, Room N663, Telephone: +61 2 9351 4352

Dr Catherine A. Leamey

Research in the Laboratory of Developmental Neurobiology focuses on how the right sets of connections form in the developing brain. Understanding these processes has important implications for the development of treatments for developmental brain disorders such as autism, Rett’s syndrome and mental retardation. Considerable recent evidence suggests that molecular determinants play an important role in regulating patterns of connectivity. As a postdoc in the USA, Dr Leamey identified a group of molecules that are differentially expressed between sensory neocortical areas during development, and are thus candidates for establishing some of the patterns of connectivity that define sensory pathways. Following up some of the genes identified forms the basis of much of the work performed in the lab to date.

The highly stereotyped nature of the mammalian visual system makes it an excellent model for studying the development of neural connections. Recent work from the lab has shown that one of the molecules discovered in the screen mentioned above, a transmembrane protein called Ten_m3, plays a key role in the development of the visual system. Most significantly, mice that lack Ten_m3 behave as if they are blind. We have shown that this is due to a requirement for Ten_m3 in the formation of aligned projections between the two eyes, and that the misaligned projections that form in the absence of ten_m3 cause a form of central blindness.

Project Title: Development and Plasticity of the Nervous System
Supervisor: Dr Cathy Leamey
Project Title:

  1. A number of projects which will continue to investigate the role of Ten_m3 in brain development using a mouse knockout model are available as Honours students.
  2. The laboratory has also developed techniques to over-express Ten_m3 locally. Analysis of the impact of over-expression is also offered as an Honours project.
  3. Other Ten_m genes are also strongly implicated in brain development. For example, Ten_m1 maps to a chromosomal locus associated with mental retardation. Projects which will begin to examine the potential roles of these molecules are available.
  4. Projects which will begin to study the spatial and temporal expression patterns of other promising candidate genes identified in the screen are available.

Other projects associated with other aspects of development, such as neural plasticity, are also available on request.

Direct enquiries can be made by email to: Dr Cathy Leamey - cathy@physiol.usyd.edu.au


BONE AND SKIN LABORATORY, Anderson Stuart Bldg, Room W222, Telephone: +61 2 9351 2561

Professor R.S. MASON and her group study the endocrine and local regulation of bone turnover and the role of vitamin D compounds in protection from UV irradiation in skin.

Current projects in bone and mineral include studies on regulation of bone turnover by calcium and other agents, including a novel osteoporosis therapy, strontium, which may act through similar mechanisms to calcium. A new project will test the hypothesis that muscle is an important storage site for vitamin D. Skin cancer is a major problem in Australia. The ongoing studies in the role of vitamin D to protect against UV damage may lead to the use of these compounds as sun-protection agents..

Project Title: Role of Vitamin D and other compounds in protection of skin cells from UV
Supervisor: Prof Rebecca S Mason
Project Description:
Our group has shown that vitamin D compounds, which are well known to be made in skin, have an important physiological function in skin to protect skin cells from the damaging effects of UV radiation. Cell death, mainly by apoptosis after UV exposure, is significantly reduced in skin cells after treatment with vitamin D metabolites. We have also shown that DNA damage is reduced in surviving cells. We now have evidence that the protective effects, including protection from UV-induced immunosuppression and photocarcinogenesis are present in mice. Preliminary studies also show a reduction in sunburn cells and DNA damage in human subjects. The project will examine likely mechanisms of action of the vitamin D compounds. These are likely to include enhanced activity of the tumour suppressor p53 and reduced nitric oxide products and a possible novel mechanism of DNA damage.

Project Title: Mechanisms of action of strontium to reduce risk of fracture
Supervisor: Prof Rebecca S Mason
Project Description:
Although strontium has been known for nearly a 100 years to increase bone mass, it has only just been released for use in the treatment of osteoporosis. It is effective in reducing both spine and hip fractures in post-menopausal women. Despite its clinical use, it is still unclear how strontium reduces fracture risk at the cellular and molecular level. Our group has shown that strontium reduces the signals for bone resorption and improves the ability of bone-forming cells to withstand stress. We have proposed that strontium acts through the receptor and cell signal pathway which mediates calcium responses in bone. Our data indicate that calcium, released from bone during resorption, acts as a bone coupling agent and a negative regulator of bone resorption. Preliminary evidence suggests that strontium, related to calcium on the periodic table, acts via a similar mechanism. The project will examine how strontium reduces bone resorption signals and examine further its capacity to enhance bone cell survival.

Project Title: Muscle as a storage site for vitamin D
Supervisor: Prof Rebecca S Mason
Project Description:
Most vitamin D is made in skin as a result of a photochemical reaction between UVB light and 7-dehydrocholesterol. The vitamin D is then converted to 25hydroxyvitamin D, the major circulating form of vitamin D, in the liver and then to the active hormone, 1,25dihydroxyvitamin D in the kidney and other tissues. Since there is relatively little vitamin D made in winter (not much UVB and not much skin exposed), a storage mechanism for vitamin D seems likely, but has not been investigated. Several lines of indirect evidence are consistent with a proposal that muscle is a site of 25hydroxyvitamin D storage and release. The project, which includes whole animal and cell culture studies, will test this hypothesis.

Direct inquiries can be made by email to: Dr Mark Rybchyn - mrybchyn@mail.usyd.edu.au or Professor Rebecca Mason - rebeccam@physiol.usyd.edu.au


ENVIRONMENTAL CONTROL OF PHYSIOLOGY LABORATORY, Anderson Stuart Bldg, Room E202, Telephone: +61 2 9351 6538

Dr Bronwyn McAllan

Animal models are frequently used to understand physiological mechanisms. Comparative Physiologists use the diverse information that can be discovered in a wide variety of non-laboratory animals to help formulate ideas about physiological processes. Current research interests have focused on the environmental control of structure and function in mammals, especially marsupials. Research areas include the photoperiodic control of reproduction, and the seasonal implications for metabolism. Other research relates to the seasonal physiological and endocrinological changes in mammals and their morphological implications. This has involved endocrine influences on non-target physiological systems, such as the renal system. Currently we are developing programmes to look at the interactions between stress, reproduction and ageing, using the small marsupials Antechinus stuartii (brown antechinus) and Sminthopsis macroura (striped-faced dunnart) as animal models.

NOTE: At present the colony of the marsupials Sminthopsis macroura and Sminthopsiscrassicaudata is based off-campus, and is unlikely to be moved to the University of Sydney before early 2008. The projects outlined below are only suitable for students wishing to start mid-2008 at the earliest.

Project Title: The regulation of reproductive physiology by environmental photoperiod
Supervisors: Dr Bronwyn McAllan
Project description:
The regulation of reproductive physiology by environmental photoperiod is poorly known in marsupials. By manipulating photoperiod and measuring reproductive outcomes in Sminthopsis macroura, including detecting hormonal changes by RIA, we can learn more about the control of seasonal reproduction in marsupials.

Project Title: The regulation of reproduction and metabolism by photoperiod and temperature.
Supervisors: Dr Bronwyn McAllan
Project description:
Seasonal changes in reproduction and torpor use (measured by open flow respirometry) are important for the survival of many small mammals. By exposing the marsupials Sminthopsis macroura and Sminthopsis crassicadata to different photoperiods and temperatures we can understand more about the survival responses of mammals to environmental change.

    Selected references
  1. Geiser, F, McAllan, B, Kenagy, G, Hiebert, S. Photoperiod affects daily torpor and tissue fatty acid composition in deer mice. Die Naturwissenschaften. 2007; 94:319-325
  2. McAllan, B, Dickman, C, Crowther, M. Photoperiod as a reproductive cue in the marsupial genus Antechinus: ecological and evolutionary consequences. Biological Journal of the Linnean Society. 2006; 87:365-379
  3. McAllan, B, Geiser, F. Photoperiod and the timing of reproduction in Antechinus flavipes (Dasyuridae: Marsupialia). Mammalian Biology. 2006; 71:129-138
  4. McAllan, B. Dasyurid marsupials as models for the physiology of ageing in humans. Australian Journal of Zoology. 2006; 54:159-172
  5. Lippolis, G, Westman, W, McAllan, B, Rogers, L. Lateralisation of escape responses in the stripe-faced dunnart, Sminthopsis macroura (Dasyuridae: Marsupialia). Laterality. 2005; 10:457-70
  6. McAllan, B, Westman, W, Joss, J. The seasonal reproductive cycle of a marsupial, Antechinus stuartii: effects of oral administration of melatonin. General and Comparative Endocrinology. 2002; 128:82-90

Direct inquiries can be made by email to: Dr Bronwyn McAllan - bmcallan@physiol.usyd.edu.au


BASIC & CLINICAL GENOMICS LABORATORY, Anderson Stuart Bldg, Room N452, Telephone: +61 2 9351 3688

Professor B.J. MORRIS and his group are elucidating molecular and cellular mechanisms of ageing and longevity, of gene expression, and of modulation of pre-mRNA splicing. The Lab is interested in longevity, cardiovascular disease, cancer and development.

Project Title: Mechanisms of longevity
Supervisor: Prof Brian Morris
Project Description:
The Lab is attempting to decipher the molecular pathways that underlie longevity by using siRNA to target key genes that when mutated in other species extend their life. We are using microarray analysis of thousands of gene expressions to see which are upregulated and which are suppressed in primary cultures of fibroblasts as they age. Importantly we are extending our research on the red wine polyphenol resveratrol that we have found suppresses molecular markers of senescence, as well as modulating expression of genes for various pathways that should extend lifespan. Identification of key genes, and thus proteins, that regulate ageing could lead to production of novel pharmaceuticals that may increase the length of human life.

Project Title: Pre-mRNA splicing
Supervisor: Prof Brian Morris
Project Description:
It is now known that the number of proteins in the human body (approx. 100,000) greatly exceeds the number of genes (approx. 23,000). Such protein diversity is achieved by alternative splicing of primary mRNA transcripts so as to include or exclude exons selectively. The Lab has identified several novel proteins that modulate alternative splicing. We are investigating more of the mechanisms involved. In so doing we are studying protein-protein interactions and functions in the nucleus, including subnuclear localization by 3D imaging microscopy, regulation of alternative splicing of primary mRNA transcripts using a range of minigenes, identification of factors in the supraspliceosome, and, in conjunction with Dr Joel Mackay's Lab in SMMBS, specific recognition sequences on RNA by SELEX.

Publication of student findings:
Publication is a high priority of the Lab and all previous Honours students have had at least one first-author paper emerge from their research. Of research publications in the past 5 years (2001-2005), 57% (20/35) were in the top 5% of journals (impact factor >3.5), as follows, in which impact factor is shown in bold: J Cell Biol 11.6 (1), Mol Cell Biol 7.8 (1), Diabetes Care 7.1 (1), Hum Mutat 6.8 (1), J Biol Chem 6.4 (2), BioEssays 6.4 (1), Hypertension 5.3 (3), J Hypertens 4.9 (4), J Mol Med 4.3 (2), J Physiol 4.3 (1), Obes Res 3.7 (2), Int J Obes 3.5 (1). Papers by Hons students in the past 4 years: 1 in J Biol Chem by a student who got 1st class Hons and University Medal, 1 by another student in J Hypertens, that attracted a special Editorial, and 1 by a further student in J Hypertens that was amongst the top 22 cited for 2005 for that journal, where in 2005 one publication in J Hypertens was the most highly downloaded article in all of the biomedical science literature and the 5th most-highly cited in science (the others being in astrophysics, particle physics and nonostructure. That publication was on Guidelines for treatment of hypertension. The most-downloaded non-Guidleines article in J Hypertens for 2005 was a single author review by Prof Morris on the molecular basis of ageing.

Direct inquiries can be made by email to: Professor Brian Morris - brianm@medsci.usyd.edu.au


EMBRYONIC STEM CELL LABORATORY, Royal North Shore Hospital, Building 10, Telepphone +61 2 9926 6482

Dr Michael Morris

Project Title: Embryonic Stem Cells
Supervisor: Dr Michael Morris
Project Description:
Embryonic stem (ES) cells are derived from the small pocket of inner cell mass cells of the very early mammalian embryo. ES cells self-renew and grow rapidly in culture and most importantly they are totipotent Ė capable of differentiating to all the different possible cell types. Therefore, they have been used widely as an excellent source of cells for studying normal and abnormal mammalian development, and for the production of specific cell types that potentially can be used in treatment of a range of human diseases.

In this lab, we are (i) mapping the signalling mechanisms which maintain ES cells in a totipotent, self-renewing, rapidly proliferating state and (ii) identifying and manipulating critical molecular switches so that ES cells lose totipotence and differentiate to specific cell types, with particular emphasis on neurogenesis.

Projects are available which draw on a variety of techniques in cell and molecular biology, protein chemistry, and bioinformatics.

Direct your enquiries to Dr Michael Morris via email: michaelmorris@med.usyd.edu.au


HUMAN REPRODUCTION UNIT, Block 3, ROYAL NORTH SHORE HOSPITAL, Telephone: +61 2 9926 7148

Associate Professor Chris O'NEILL's laboratory undertakes research in four broad themes. Honours projects are available in each as follows:

Project Title: Reproduction
Supervisor: A/Prof Chris O'Neill
Project Description:
  1. The regulation of fertilization - changes in sperm function in preparation for fertilization
  2. Signal transduction by survival factors and mitogens in the early embryo
  3. The consequences of assisted reproductive technology (e.g. IVF) on the health of offspring and across generations
  4. Proteomic analysis of the factors that control to embryo viability
Project Title: Development
Supervisor: A/Prof Chris O'Neill
Project Description:
  1. The regulation of epigenetic reprogramming during embryo development
  2. Characterization of the transcriptome coding for pluripotency
  3. The regulation of embryonic diapause in the mouse and wallaby
Project Title: Stem Cells
Supervisor: A/Prof Chris O'Neill
Project Description:
  1. Regulation of formation of embryonic stem cell lineages by embryos produced by IVF
  2. Development of disease models for neurodegenerative diseases using embryonic stem cells
  3. Development of embryonic stem cells for toxicology assays to reduce use of animals in research
  4. Proteomic analysis of communication between embryonic stem cells
Project Title: Cancer
Supervisor: A/Prof Chris O'Neill
Project Description:
  1. Epigenetic regulation of gene expression during oncogenesis
  2. Experimental and epidemiological assessment of the risks of cancer in IVF progeny.

Direct your enquiries to Associate Professor Chris O'Neill via email: chriso@med.usyd.edu.au
Faxed enquiries can be sent to: +61 2 9906 1872.


MOLECULAR NEUROSCIENCE LABORATORY, Anderson Stuart Bldg, Room N343, Telephone: +61 2 9351 4598

Dr W.D. PHILLIPS

Project Title: Structural changes at the nerve-muscle synapse in a mouse model of anti-MuSK Myasthenia Gravis
Supervisors: Dr Bill Phillips and Louise Cole
Project description:
Muscle Specific Kinase (MuSK) is a receptor tyrosine kinase in the postsynaptic membrane of the neuromuscular synapse. MuSK is essential for synapse formation during embryonic development. Furthermore autoimmune antibodies against MuSK cause a very severe form of Myasthenia gravis in adults. This Honours project will use light and electron microscopy to identify changes in the structure of the neuromuscular synapse in a newly-developed mouse model of the disease. This should help us better understand the role of MuSK as a regulator of the health of synapses.

Project Title: MuSK signaling and synapse modification
Supervisors: Dr Bill Phillips
Project description:
Another way of studying the function of MuSK in the homeostasis of the neuromuscular synapse is to introduce a mutant form of the protein into cells. This Honours project will test the effect of an expression plasmid encoding MuSK fused to jellyfish green fluorescent protein upon synaptic differentiation. Wild-type (control) and a signaling-defective mutant form of MuSK (experimental) will be transfected into cultured muscle cells and electroporated into adult mouse muscles to study the effect of inhibiting MuSK signaling upon the postsynaptic acetylcholine receptor cluster.

Contact Bill Phillips direct by email:Dr William Phillips - billp@physiol.usyd.edu.au or phone +61 2 9351 4598 for more information and background reading on the project
Faxed enquiries can be sent to +61 2 9351-2058


VISION LABORATORY, Anderson Stuart Bldg, Room N659, Telephone: +61 2 9351 3928

Dr Dario Protti

The vision laboratory is interested in understanding how the images of the visual world are converted in neural information and how this information is represented in the brain. Vision starts in the retina, where light is converted into an electrical signal. Within the retina, a large number of neurons are interconnected in different ways giving rise to multiple networks specialised for specific functions. Each of these networks utilise specific channels and neurotransmitter receptors to shape light signals, which will carry information about particular features of the visual world to the rest of the brain. Several vision disorders, such as night blindness, have been associated with malfunction of membrane channels or with signal transmission in the retina.

We are also interested in the cellular mechanisms responsible for the adaptive changes that take place when the visual system is exposed to large changes in light intensities. The retina is able to change its activity in response to both short-term and long term changes and several different mechanisms have been proposed.

Project Title: Contrast adaptation
Supervisors: Dr Dario Protti
Project description:
Contrast adaptation is a phenomenon by which the retina adapts to different ranges of light intensity around the mean. In this project, you will examine the neural mechanisms underlying the generation of contrast adaptation in retinal ganglion cells.

Project Title: Plasticity phenomena in the nervous system
Supervisors: Dr Dario Protti
Project description:
Plasticity phenomena in the nervous system are mediated by several neurotransmitters and receptors. In this project, you will study the role of specific neurotransmitter systems in the modulation of synaptic transmission and synaptic plasticity in the visual system.

Experiments involve the use of the following techniques:

Direct enquiries can be made by email to: Dr Dario Protti - dariop@physiol.usyd.edu.au


SYSTEMS NEUROSCIENCE LABORATORY, Anderson Stuart Building.

Dr Atomu Sawatari

A fundamental assumption in the field of neuroscience is that the brain formulates our perception of, and interactions with our surroundings. Systems neuroscience employs a variety of approaches, from genetic analysis, through anatomical and physiological methods, to behavioral assessment of the whole animal to determine how this complex organ manages to do this. The goal of the newly formed Systems Neuroscience Laboratory is to attempt to understand the neural mechanisms that underlie perception and behavior. We employ a host of in vitro and in vivo techniques (some in collaboration with other laboratories) to achieve our aim. A special emphasis will be placed on revealing the functional neural circuits in brain areas known to be involved in visual perception, and the processing and execution of behaviors relevant to an organismís interaction with its environment.

Project Title: Revealing neural circuits underlying volition
Supervisors: Dr. Atomu Sawatari
Project Desription:
We are interested in elucidating the neural circuits involved in the execution of volitional or self initiated action. Of particular interest are changes that occur in specific cell types within the basal ganglia during critical developmental epochs.
Two projects are offered in this area:

Project Title: Determining the source of visual deficits in Ten-m3 KO mice
Supervisors: Dr. Atomu Sawatari and Dr. Catherine Leamey
Preliminary evidence suggests that Ten-m3 KO mice suffer from severe visual behavioral deficits. In collaboration with Dr. Leamey and members of her research group, we hope to determine the cause of this impairment by conducting a thorough and detailed anatomical, physiological, and behavioral assessment of the mutant animalís visual system. Projects involved in this collaboration will be available.

Direct enquiries can be made by email to:Dr Atomu Sawatari - atomu@medsci.usyd.edu.au


LABORATORY OF VISION & COGNITION Anderson Stuart Bldg, Room E501, Telephone: +61 2 9036 9926

Dr Sam Solomon

Our research is concerned with how the brain analyses, and makes decisions about, the sensory information it receives. To understand this we study the visual system, the primary sense organ in primates, and the one that we know most about. In physiological experiments we characterise at the level of nerve cells the work done by the eye and visual cortex. In perceptual experiments we explore performance, and compare these observations with the physiological ones through quantitative analysis. We are part of the School of Medical Sciences and also invite interested students from, for example, the School of Psychology or School of Engineering, as long as you meet the criteria for acceptance to Honours here.

I encourage students to participate in any and all aspects of the lab's research, within a couple of months targeting a question you find interesting. The question can be novel or part of the ongoing research, as long as we can answer it.

Project Title: Cortical mechanisms of motion detection
Supervisors: Dr Solomon, Dr Tailby
Project Description:The detection and discrimination of moving surfaces is necessary for any interaction with the external environment, and is especially important in controlling eye movements. Using extracellular recordings from visual cortex, and anatomical tracing techniques, your project will be investigate the neural mechanisms that code visual motion.
Feel free to contact Dr Sam Solomon samuels@physiol.usyd.edu.au to see if this fits your interest.

Project Title: Constraints on information flow through the visual thalamus
Supervisors: Dr Solomon
Project Description: The optic nerve consists hundred of thousands of axons that form several parallel pathways, the main ones coursing through the thalamus to primary visual cortex; from this the brain must interpret the outside world. What information about the outside world is provided by the signals of neurons that provide the input to visual cortex? How much of the signals provided by an individual neuron are redundant, present in the signals of other neurons? Your project will use extracellular recordings from the lateral geniculate nucleus of the thalamus, simultaneously recording from multiple electrodes, to determine this.
Contact Dr Sam Solomon Dr Sam Solomon samuels@physiol.usyd.edu.au if you might be interested.

Project Title: Functional properties of visual brain areas in mice suffering abnormal cortical development
Supervisors: Dr Solomon, Dr Camp
Project Description: Your project will use in vitro and in vivo methods to study the functional organisation of visual cortical pathways in a knockout mouse model of abnormal cortical development. The visual pathway is the best understood of all cortical processes; by comparing its functional properties in these knockout mice and their wildtype counterparts, we can begin to understand how abnormal cortical development has an impact on neural processing.
Contact Dr Aaron Camp aaronc@physiol.usyd.edu.au or Dr Sam Solomon samuels@physiol.usyd.edu.au if you might be interested.

The laboratory publishes in high quality journals (since 2001 articles have appeared in Nature, Neuron, The Journal of Neuroscience, The Journal of Physiology) and is committed to helping students do the same (I'm not that far from being one myself).