The projects listed below are available to "Honours" candidates in 2004. These one-year research programs are available ina number of programs which can accommodate a wide range of students. Thecurrent year Honourshome 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:

• Muscle Cell Function Laboratory - Professor D.G. Allen
• Neurobiology Laboratory - Professor M.R. Bennett
• Auditory Neuroscience Laboratory - Associate Professor S. Carlile
• Epithelial Transport Laboratory -  Professor D.I. Cook
• Cardiovascular Neuroscience Laboratory - Professor R.A.L. Dampney
• Laboratory of Developmental Physiology - Dr M. Day
• Muscle Research Laboratory - Dr J.F.Y. Hoh
• Cortical Development Laboratory  - Dr C. Leamey
• Bone & Skin Cell Laboratory - Associate Professor R.S. Mason
• Basic & Clinical Genomics Laboratory - Professor B.J. Morris
• Human Reproduction Unit, RNSH - Associate Professor C. O'Neill
• Molecular Neuroscience Laboratory - Dr W.D. Phillips
• Hypertension and Stroke Research Laboratories- Associate Professor P. Pilowsky
• Vision Laboratory - Dr D. Protti
  
• External Honours Projects

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

 Two principal research areas:
(i) 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.

 (ii) 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: simonc@physiol.usyd.edu.au

EPITHELIAL TRANSPORT LABORATORY, Anderson Stuart Bldg, Room N401, Telephone: +61 2 9351 2809

Projects available in  Professor D.I. COOK's laboratory:
Honours projects:

1. 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.
2. Identification of novel regulators of sodium channels.
This project will use the yeast 2-hybrid technique to identify novel proteins regulating sodium channel activity.
3. 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.
&nbs p;4. 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
5. 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 : davidc@physiol.usyd.edu.au

The general theme of research in Professor R.A.L. DAMPNEY's lab is the control of blood pressure and sympathetic nerve activity bythe brain. Research projects could be in one of the following areas:

1. Central mechanisms maintaining tonic sympathetic vasomotor activity and resting blood pressure.

2. Role of novel receptors in the brain in the regulation of blood pressure

3. Role of hypothalamic nuclei in the regulation of blood pressure

4. Actions of circulating angiotensin II on the brain: role in blood pressure regulation.

[The levels of circulating angiotensin II are increased in heart failure and some types of hypertension. This is believed to be a major factor leading to the increased sympathetic activity in these conditions]

5. Actions of circulating leptin on the brain: role in blood pressure regulation.

[The levels of circulating leptin, which is a hormone released from fat tissue, is increased in obesity. This is known to lead to increased sympathetic activity, which could be a major factor causing obesity-related hypertension].

Telephone: +61 2 9351 6533

2. Expression of members of the ether-a-gogo K+ channel family during development
Eag K+ channels are over-expressed in some types of cancer cells and their inhibition can block cell proliferation. We have shown that these channels are expressed in the early mouse embryo and are currently studying their role in cell division and embryonic development.

3. Formationof the first epithelium in the embryo
We are using a trophoblas t stem cell line to study how ion channelsare involved in formation of the trophectoderm, which is the first transporting epithelium in the embryo.

Techniques used inthese projects:

* molecular biology eg. RT-PCR, cloning
* biochemical techniques eg.Western blotting, immunofluorescence
* Antisense and pharmacological knock out of gene expression
* Cell culture
* Embryo manipulation
* electrophysiological techniques eg. patch-clamping
 

Direct enquiries can be made by email to: margotd@physiol.usyd.edu.au  

MUSCLE RESEARCH LABORATORY, Anderson Stuart Bldg, Room E501, Telephone: +61 2 9351 4267

Correlation of mechanical properties of extraocular muscle fibres with myosin heavy chain composition

Extraocular muscle fibres are complex with regard to their myosins composit ion. They contain several myosins in addition to those found in limb muscles. Of particular interest is the EO-specific isoform which is believed to confer high speed of cross-bridge cycling, but this has not been firmly established. Previous work has shown that EO fibres have dynamic stiffness minimum frequencies (fmin) from 4-33 Hz whereas those of limb fibres have a narrower range (10-26 Hz). This project is to test the hypothesis that EO containing fibres are responsible for the high end of the fmin range (27-33 Hz). Single fibres will be teased out from glycerinated rabbit EO muscle fibres, and fibres containing EO myosin will be identified by immunohistochemistry using monoclonal antibodies against EO and other isoforms of myosin on a small fragment of the fibre. The fmin of identified fibre will then be measured using sophisticated equipment under computer control.

Direct enquiries can be made by email to: joeh@physiol.usyd.edu.au

CORTICAL DEVELOPMENT LABORATORY, Anderson Stuart Bldg, Room N663, Telephone: +61 2 9351 4352

The focus of interest in Dr Catherine A. Leamey’s laboratory is to understand how different neocortical areas, characterised by their distinct patterns of cytoarchitecture and connectivity, form during development.  A number of recent studies have provided evidence that molecules that are expressed in gradie nts in the developing cortex may play important roles in regulating the subsequent differentiation of cortical areas.  My own recent work has used high-density microarrays (or Genechips) to identify a group of candidate genes that are differentially expressed between cortical areas.  Follow up work has found that some of these genes show extremely interesting expression patterns, which are consistent with the possibility that these molecules could play important roles in regulating cortical development and this possibility is being investigated. 

Honours projects include:
1) Projects which will begin to study the spatial and temporal expression patterns of some of the novel candidate genes in mice.  These studies would involve performing in situ hybridization, immunohistochemistry and anatomical tracing experiments.

2) Projects which will begin to examine the anatomical consequencesof under-expression of some of the candidates that are already being studied in the lab are also available.  This work will use anatomical techniques to study the formation of pathways in knockout mice that lack the genes of interest.

3) The marsupial mammal the wallaby provides an excellent model forinvestigating cortical development, since it is born at a very early stageof cortical development and then develops over a protracted period whereit is accessible in the pouch.  Although the anatomical and physiologicaldevelopment of this mammal has been studied in detail, nothing is knownabout the molecules which may regulate this.  This project will usemolecular biological techniques to investigate whether molecules known tobe important in placental mammals are expressed in the wallaby, and if soto determine what their expression patterns are.  The work will mostlikely be combined with anatomical tracing studies.  Apart from providingimportant data about molecular control of cortical development, this projectmay also provide data that is interesting from an evolutionary perspective.

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

Current projects in bone and mineral include studies on themechanisms of corticosteroid-induced osteoporosis, bone cell actions of phytoestrogensand characterisation of a novel phosphate regulating hormone. The area ofskin research interest is mechanisms of skin cell protection from ultravioletirradiation and ways of enhancing this. There are two honours projects offeredfor 2004.

"Role of Vitamin D and other compounds in protection ofskin cells from UV"
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 both human keratinocytes (epidermal cells) and melanocytes (pigment cells) after treatment wit h vitamin D metabolites. We have also shown that DNA damage is reduced in surviving cells. We now have preliminary evidence that the protective effects arepresent in human subjects and in mice. The project will examine some likelymechanisms of action of the vitamin D compounds and the possible involvementof other skin cell-produced compounds which may potentiate this effect.

Direct enquiries can be made by email to: rebeccam@physiol.usyd.edu.au


"The role of sympathetic nervous system control in bone cell function"
Maintenance of bone mass involves the complex interplay of bone formation by osteoblasts (OBs) and bone resorption by osteoclasts.  Recent evidence indicates that the central nervous system plays a role in determining bone mass by a mechanism which involves a direct effect of neurotransmitters and modulators of the sympathetic nervous system (SNS) on bone cell function. Rodent studies have demonstrated that b-adrenergic agonists inhibit bone formation as measured by bone volume, rate of bone formation and OB number. Human studies have not been carried out.  Using an established cell culture model of human OBs, the research will assess the direct effect of sympathomimetic molecular regulators on differentiation, proliferation and life span in human OBs treated with specific b-2 agonists, b-2 adrenergic receptors (AR) antagonists, the natural ligand of b-AR, as well as a non-specific b-AR antagonist.  This work may contribute to a novel approach to the treatment of osteoporosis.

Direct inquiries can be made by email  to: mmmuir@physiol.usyd.edu.au or rebeccam@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 study genes that might have a role in cardiovascular disease, particularly hypertension. The Lab is also elucidating basic mechanisms of gene expression. Some of this has relevance to development and cancer and longevity.

Regulation of  human renin expression: by gene transfer, DNA-protein binding analyses, yeast 3-hybrid to isolate factors that control mRNA stability, gel shift, UV cross-linking, western blots, siRNA, and yeast 2-hybrid to isolate protein-protein interactors.

Molecular genetics of hypertension: (1) Genome scanning using microsatellite markers in affected human sibpairs. (2) Candidate gene analyses.

Protein interactions and functions in the nucleus: subnuclear localization by 3D imaging microscopy,  regulation of alternativesplicing of primary mRNA transcripts (a major interest in arriving at thenumber of proteins in the body of 100,000, despite there being only 35,000genes), etc.

Mechanisms of longevity:  We plan to decipher the molecular pathways that underly longevity by using siRNA to target keygenes that when mutated in other species extend their life. We will usemicroarray analysis of thousands of gene expressions to see which are upregulatedand which are suppressed. This could lead to production of novel pharmaceuticals that may increase the length of human life.

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. Over the past 7 years the Lab has published over 50 papers injournals that include Nature Genet (29.6),J Cell Biol (impact factor 14.0),  Hum Mol Genet (9.3), BioEssays (8.5), 3 in J Biol Chem (7.5), 7 in Hypertension (5.3), Brit Med J (6.6),  2 in Hum Mutat (6.1 ), Diabetes Care 5.4 (1), Am J Physiol (Renal) 4.5), 2 in J Hypertens (4.2), Cancer Epidem Biomar Prev 4.0 (2), J Mol Evol (4.0), 2 in J Mol Med (3.5), Obes Res (3.4), Int J Obesity (3.2), 4 in Am J Hypertens 2.8 (4),2 in  Am J Med Genet (2.4).

Papers by Hons students in the past 3 years:  1 in J Biol Chemby a student who got 1st class Hons and University Medal, and 1 by another student in J Hypertens, that attracted a special Editorial.

Direct inquiries can be made by email  to: brianm@physiol.usyd.edu.au

Honours Projects 2004

The Human Reproduction Unit undertakes a range of projects investigatingthe physiological basis of:
(1) The regulation of fertilization,
(2) The survival and growth of the early embryo (particularly after theirproduct ion by in vitro fertilization and related methods),
(3) The consequences of aberrations in early embryo growth on fetal and neonataldevelopment
(4) The control of survival and differentiation of embryonic stem cells.

There are a number of studies suitable for honours projects in each of these4 broad themes.

Projects in the Human Reproduction Unit involve extensive use of:

•  Tissue culture methods (particularly embryo culture);
•  In vitro fertilization, embryo micromanipulation, nucleartransfer and embryo transfer
•  Embryo manipulation including micromanipulation;
•  Microscopy (including confocal microscopy);
•  Molecular analysis – PCR, QRTPCR, western blotting, immunoprecipitation;
•  Molecular transfection;
•  Real time monitoring of protein expression; and
•  Use of genetically modified organism as models.

Direct your enquiries to A/Professor O'Neill via email, by clicking this link: chriso@med.usyd.edu.au

Projects available in Dr W.D. PHILLIPS' laboratory:

Regulation of gene expression at synapses
One important way in which synapses can grow and remodel is by ensuring that the messenger RNAs for synaptic proteins are localized immediately under the postsynaptic membrane. This can help to control where synaptic proteins are made and how and when they are put together. Synapses must be able to respond to injury and disease. In the case of the nerve-muscle synapse it is known that the gene for the postsynaptic acetylcholine receptor is strongly up-regulated if the muscle cell is deprived of its normal patterns of action potentials. Our recent work suggests that the level of expression of proteins that associate with the acetylcholine receptor may influence the organisation of the synapse. If this is true, then modifying expression of proteins like rapsyn might offer a potential alternative way to treat those suffering from disorders that make the acetylcholine receptors unstable at their synapses. This project will use techniques such as laser-capture micro-dissection and quantitative reverse transcriptase/PCR to study how the expression of synaptic proteins at the synapse respond to changes in synaptic transmission and to altered expression of other genes.
Contact Bill Phillips direct via email: billp@physiol.usyd.edu.au or phone 9351-4598 for more information and background reading on the project.

Regulation of the subcellular targeting and functional properties of rapsyn by tyrosine phosphorylation
Rapsyn is a protein that binds to the acetylcholine receptor in skeletal muscle. Rapsyn is involved in intracellular trafficking of acetylcholine receptors (AChR) to synapses. A number of protein kinases and phosphatases are thought to be involved in controlling the formation and modification of synapses. The aim of this project is to determine how phosphorylation of specific amino acid residues within rapsyn might regulate targeting of rapsyn to particular organelles and membranes within the cell. This project will develop skills and experience in molecular biology techniques as well as immunocytochemistry, cell culture and confocal microscopic imaging.
Contact Bill Phillips direct by email: billp@physiol.usyd.edu.au or phone 9351-4598 for more information and background reading on the project.

HYPERTENSION AND STROKE RESEARCH LABORATORIES, Royal North Shore Hospital, Ground Floor Block 3, Dept of Physiology, University of Sydney and Dept of Neurosurgery, Royal North Shore Hospital. Telephone: +61 2 9926 8080.

Associate Professor P. PILOWSKY (Head), and his group(Prof John Chalmers, Prof Michael Morgan, Dr Ann Goodchild, Dr Qi-Jian Sun.)conduct basic research studies that are aimed at understanding the role ofthe central nervous system in the control of blood pressure, airways andbreathing: the ABC of medicine. In particular, we are interested in the interactionsbetween these vital systems, the function and morphology of the neurons thatcontrol them and the neurotransmitters and other neuromodulators that theycontain or release. In addition, we compare normal animals with those thatare hypertensive in order to see if differences are present. An eclecticrange of techniques is used in these studies, depending on the questionsto be addressed. These include extracellular and intracellular electrophysiology,intrathecal and intramedullary drug administration and immunocytochemistry.

  In general we believe that students should have the opportunity to explore - briefly - a range of topics before settling on one. Some people have a particular aptitude for different tec hniques. Given the broad spectrum available - from anatomy to molecular biology - we are able to accommodate most individuals. Here we list some of the available projects. Naturally the specifics of these may change between now and 2004.
 

• Peptidergic control of neurons in the brainstem that control blood pressure.
• Amino acids that control sympathetic outflow.
• Role of AMPA receptors in the control of blood pressure.
• Gene expression in experimental hypertension.
• Gene expression in response to manipulations that affectblood pressure.
• Tract-tracing studies of the pathways that control bloodpressure.
• Studies of the pathways that control breathing.
• Neurotransmitter systems that control sympathetic neurons in the spinal cord.
• Control of sympathetic neurons following spinal cord injury.
• Second messenger pathways in cells that control blood pressure.

We strongly urge interested students to make contact (by email or phone (99268080) and ask for Paul Pilowsky or Ann Goodchild)
For more information about poject see: http://www.physiol.usyd.edu.au/pilowsky/projects2001.html and/or contact Paul Pilowsky on +61 2 9926 8080 or by email to pilowsky@med.usyd.edu.au

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

Dr Dario Protti’s laboratory is focused on the study of different neuronal circuits which are concerned with the analysis of singular aspects of the visual world.
Particular features of visual stimuli are conveyed to the brain viaseparate pathways, which utilise specific channels and neurotransmitterreceptors to shape light signals. A clear example of signalling throughdifferent pathways is the existence of a neuronal network devoted to signallingat low light levels (scotopic or rod circuit) whereas another network exclusively transmits signals at high light levels (photopic or cone circuit).
We are particularly interested in the changes that take place during the switch from nighttime to daytime vision. This transition is strongly influenced by the neurotransmitter dopamine, which acts as a light signal.

Projects in the following areas of research are available for Honours projects:

• Modulation of voltage-gated calcium currents in AII amacrine cells by dopamine.
• Role of voltage-gated sodium channels in light responses of AII amacrine cells.
• Characterisation of the AII amacrine‡OFF-cone bipolar cell synapse and its modulation by neurotransmitters and neuromodulators.

Experiments involve the use of the following techniques:

• Patch-clamp recordings in retinal slices
• Intracellular staining and morphological reconstruction

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