Summer Vacation Studentships

The Queensland Institute of Medical Research is one of Australia's leading medical research institutes. Situated on the campus of the Royal Brisbane Hospital and the University of Queensland Medical School in Herston, QIMR offers a stimulating multi-disciplinary environment for research training.

QIMR offers studentships of 4-6 weeks duration in the summer vacation. Successful applicants will receive an allowance of up to $250 per week. Preference will be given to undergraduates who will have completed their second year in a science, medical, dental or veterinary degree in Australia by December.

The studentships offer students the opportunity to work in a research environment, to learn new techniques and to participate in a defined research project with supervision.

Application details click here

---

Membrane Transport Laboratory
Dr Nathan Subramaniam
Phone: 3362-0179
Email: Nathan.Subramaniam@qimr.edu.au

Membrane Transport

In recent years it has become very evident that a large number of human disorders can be attributed to defects in the trafficking and localisation of molecules, predominantly membrane proteins. By studying how mammalian cells regulate the synthesis, assembly, trafficking and localisation of membrane proteins implicated in these human disorders we hope to advance our understanding of these disorders with the prospect of a better therapeutic intervention.

HFE, transferrin receptor 2, ferroportin1 and hepcidin are four proteins which have been implicated in iron metabolism. Mutations in these four proteins have been shown to cause iron overload in humans.

A number of exciting projects are available in the laboratory. These include:

1. Molecular and cellular analysis of hepcidin and hemojuvelin

Hepcidin and hemojuvelin are genes found to be mutated in juvenile haemochromatosis. The role of hemojuvelin in iron regulation is still unknown. Using a variety of molecular and cellular biology tools we will study the synthesis, assembly, trafficking and regulation of hemojuvelin and hepcidin. Using proteomics we will identify molecules which interact with hemojuvelin with the ultimate aim of understanding the role of hemojuvelin and these proteins in regulating iron absorption and transport.
2. Studying the mechanism by which SNAREs influence trafficking of membrane proteins

Receptors on both exocytic and endocytic vesicles, termed SNAREs, and a number of adaptor molecules have been shown to influence the trafficking and localisation of membrane proteins. We are studying the role of these proteins in the trafficking of HFE and transferrin receptor 2. Both these proteins are expressed on the cell surface. Studies are aimed at studying the regulation and internalization of these molecules.
3. Molecular and functional characterisation of a novel ubiquitin-like protein

We have recently identified a novel ubiquitin-like protein with homology to yeast proteins involved in protein degradation and DNA-damage repair. We have also identified a related homolog. Studies have been initiated at understanding the role of these mammalian proteins in these processes. This project would analyse the expression and distribution of these proteins using real-time RT-PCR in various tissues and cell lines. Proteomics will be used to identify interacting molecules. These molecules will then be cloned and characterized. Using the yeast protein as a model the interaction of candidate proteins will be studied.

Radiation Biology & Oncology Laboratory
Dr Olivier Becherel
Phone: 3362-0337
Email: Olivier.Becherel@qimr.edu.au

Ataxia with oculomotor apraxia in DNA damage response and RNA metabolism

Ataxia oculomotor apraxia (AOA) is a common phenotype found in several degenerative disorders of the nervous system. Ataxia refers to lack of coordination and oculomotor apraxia describes the difficulty in moving the eyes. These debilitating diseases include ataxia-telangiectasia (A-T), A-T like disorder (A-TLD), both of which are characterized by a defective response to DNA damage and cancer predisposition, and ataxia oculomotor apraxia type 1 (AOA1) and type 2 (AOA2).

The gene mutated in AOA1, APTX, was identified in 2001 and encodes for aprataxin, a novel protein involved in DNA repair/DNA damage processing. In the case of AOA2, the gene mutated, SETX, was recently discovered and encodes for senataxin, a novel protein predicted to contain a seven-motif domain at its C-terminus, typical of the superfamily I of DNA/RNA helicases. Preliminary results on senataxin and recent data on aprataxin suggest a potential role of these two proteins in the repair/processing of DNA breaks and RNA metabolism.

To gain further insight and ultimately pinpoint their cellular roles during the response to DNA damage and in RNA metabolism, several studies are under way, such as:

1. Role of senataxin in DNA transcription and mRNA splicing (localisation, dynamics and splicing efficiency)
2. Down-regulation of genes mutated in recessive spinocerebellar ataxias by stable small interfering RNA
3. Cloning and expression of GST-fusion proteins for protein-protein interaction studies

A panel of methods are used in the various aspects of the study and include classical molecular biology techniques (e.g: cloning, PCR), biochemistry (e.g: protein expression and purification, analysis of protein-protein interactions), cell culture, and cell biology (e.g: microscopy, immunofluorescence).

Indigenous Health Research Program
Dr Patricia Valery
Phone: 3362-0224
Email: Patricia.Valery@qimr.edu.au

Obesity and type 2 diabetes in indigenous and non-indigenous children

The project I have in mind is one looking at obesity in Indigenous children in the Torres Strait. We have data on 350 children (46% overweight or obese), about 15% have the metabolic syndrome, 5% have diabetes type 2.

This data is already in a research paper (under review at the moment) but we also had some results from urine tests and blood pressure (69 had proteinuria and 24 of those were also hypertensive) that we have not included on this paper.

The student would analyse this data and write a short communication paper or letter on the topic including a systematic literature review.

Iron Metabolism Laboratory
Dr Greg Anderson
Phone: 3362-0187
Email: greg.anderson@qimr.edu.au

Intestinal Iron absorption

The main focus of the lab is to understand the biology of the essential trace element iron. In particular, we are interested in the mechanism and regulation of intestinal iron absorption and human disorders where iron homeostasis is perturbed.

Iron is not only essential, it is toxic when present in large amounts, so the amount of iron in the body must be tightly regulated. One of the most important regulatory stimuli is oxygen. The natural physiological response of the body to low oxygen concentrations is to increase intestinal iron absorption. This is because low oxygen signals the body to produce more haemoglobin, and iron is essential for haemoglobin synthesis.

To facilitate the oxygen-dependent changes in iron absorption, the genes encoding a number of the proteins either involved in the passage of iron across the small intestinal epithelium or its regulation are themselves regulated by iron. However, we know very little about the mechanism by which iron alters the expression of these genes. Two of these form the basis of potential Honours projects.

1. Regulation of hepcidin by oxygen

Hepcidin is a small peptide produced by the liver that has emerged in recent years as a central regulator of body iron metabolism. It acts to repress iron release into the circulation from intestinal epithelial cells, macrophages and other cell types. Under hypoxic conditions, hepcidin gene expression is decreased leading to reduced hepcidin synthesis and increased iron absorption.

2. Regulation of haem carrier protein 1 (HCP1) by oxygen

HCP1 is a candidate haem transporter in the small intestine that is thought to be responsible for the absorption of haem iron from the diet. Its expression, in contrast to that of hepcidin, is increased under hypoxic conditions such that the absorption of haem iron is increased when required.

The goal of each of these studies is to identify elements in the promoters of the two genes that are responsible for its regulation in response to changes in oxygen levels. Standard promoter analysis methods will be carried out using either the hepatoma cell line HuH7 (for hepcidin) or the intestinal cell line Caco-2 (for HCP1) as model systems.

These projects will give the student experience in cell culture, subcloning and manipulating DNA, promoter reporter assays and gene expression. They will also provide the student with an appreciation of the biology of both iron and oxygen.

Scabies Laboratory
Dr Angela Mika
Phone: 3362-0417
Email: Angela.Mika@qimr.edu.au

Scabies

Scabies is a disease of national and worldwide importance caused by burrowing of the ectoparasitic mite Sarcoptes scabiei into the epidermis. Until very recently no molecular studies on scabies had been done because of the difficulty of obtaining or culturing mites. We have solved this problem by constructing a library of expressed S. scabiei sequences from mites obtained from skin shed into the bedding of patients with the severe form of the disease, crusted scabies.

Over 40,000 of these clones have been sequenced by our group providing for the first time a great amount of molecular data on this parasite and a major resource for future studies. To identify targets for protective intervention against scabies, this database has been searched for molecules involved in parasite survival. Molecules that are localized in the gut are of special interest because they could serve as vaccine candidates or drug targets. The homologues of major allergens of the house dust mites (which are closely related to scabies mites but already extensively studied since they play a role in asthma) are of special interest.

We have identified a complex scenario of several families of proteases and protease inhibitors. We are currently exploring the structures and functions of these proteins with the aim to interfere with them and thereby with the mite's survival.

If you join our project you will be exposed to a wide range of research including parasitology, molecular biology, protein biochemistry, enzyme and structural biology.

We are interested in SVS, Hons, Masters/PhD

Conjoint Gastroenterology Laboratory
Dr Kevin Spring
Dr Barbara Leggett
Phone: 3362-0487
Email: Kevin.Spring@qimr.edu.au

Genetic and Epigenetic characterization of Colorectal Cancer

Colorectal cancer is the most common form of cancer in Australia. Our laboratory focus is on a subset of colorectal cancer that is characterized by microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP).

These cancers develop from colorectal polyps via the serrated neoplasia pathway and we wish to identify the key epigenetic and genetic defects involved in the initiation and progression of these cancers.

Potential projects will focus on the characterization of precursor lesions (polyps) and cancers and assessing potentially important target genes for mutations or epigenetic silencing of gene expression.

Clinical Haematology Laboratory
Dr Maher Gandhi
Phone: 3845-3792
Dr Jamie Nourse
Phone: 3845-3134
Email: Jamie.Nourse@qimr.edu.au
Maher.Gandhi@qimr.edu.au

Response to rituximab in immune thrombocytopenic purpura

Adult immune thrombocytopenic purpura (ITP) is an autoimmune condition associated with frequent relapses and / or refractoriness to initial therapy such as steroids, intravenous immunoglobulin and splenectomy.

Summary

ITP occurs as a result of autoantibodies against the patients' own platelets, producing thrombocytopenia which predisposes the patient to bleed. Accelerated destruction of platelets is mediated by the reticuloendothelial system via the activity of FcGamma Receptor bearing phagocytic cells.

We hypothesize that polymorphisms of the FcGamma receptors are involved in the pathogenesis of ITP, and are likely to be implicated in the response of ITP to the monoclonal antibody rituximab. We have teamed up with hospitals across Australia to evaluate the benefit of rituximab in patients with relapsed / refractory ITP.

Being involved with this prospective study has given us access to a large (over 100) uniformly treated group of ITP patients. This is an invaluable resource with which to study scientific aspects of ITP: specifically the genetic determinants which influence susceptibility to ITP and the mechanisms by which rituximab works in ITP.

Research Aims

a) To determine the incidence of FcGamma Receptor polymorphisms in adult ITP. b) To assess the impact of FcGamma Receptor polymorphisms on the efficacy of rituximab. Ours will be the largest study to examine FcGamma receptor polymorphisms in adult ITP to date, the only one to study a uniformly treated population and the only study to correlate the data with therapeutic response. Accrual is on target for completion by 2009.

Work involved

Determination of the frequency of FcGamma Receptor polymorphisms in a healthy control population, comprising 100 volunteers. We need this to make sense of the data in our patient population. The work will involve obtaining samples (buccal scrapes) from volunteers, DNA extraction, and PCR. Obtaining the buccal scrapes should take no more than a few days. The assays involved are already up and running and lend themselves to the time constraints of a summer vacation student: i.e. since DNA is so stable, they can be performed as and when time permits. They also lend themselves to being done in batches.

Type of candidate we are looking for: Someone who is motivated, efficient, friendly and can keep meticulous laboratory records. Prior experience of PCR is not essential, as hands on training will be given.

What's in it for you

1. You'll work in a pleasant, friendly supervised environment.
2. An opportunity to perform research that lends itself to flexibility: necessary given your time constraints.
3. You will gain experience of applied scientific research.
4. There is a strong possibility that the results generated will advance medical knowledge of a debilitating condition and result in your being a co-author in a good medical publication.

Bacterial Pathogenesis Laboratory
Dr David McMillan
Phone: 3845-3712
Email: David.Mcmillan@qimr.edu.au

The Bacterial Pathogenesis Laboratory conducts research into beta-hemolytic streptococci, a group of bacteria that cause a wide range of diseases in humans. We currently have two projects available that would suit enthusiastic Honours students. Smaller aspects of these projects are also available to Summer students who would like to gain experience in a research laboratory.

Multi-locus sequence typing of group G streptococcus (GGS)

Normally considered a commensal organism or opportunistic pathogen, several studies have now demonstrated that GGS is able to cause a range of diseases in humans. The virulence factors that enable GGS to cause these diseases are unknown. It is also unknown whether GGS strains capable of causing disease comprise a distinct evolutionary lineage from those strains incapable of causing disease.

In this project Multi Locus Sequence Typing (MLST) will be used to determine the evolutionary relationships between multiple GGS isolates. An MLST profile for an individual strain is created by nucleotide sequencing seven conserved house-keeping genes, that are not be the subject of evolutionary pressure. Our laboratory has a collection of clinically defined GGS isolates collected from patients presenting with invasive disease. We also have a collection of non-disease associated GGS isolates. MLST will be used to investigate the evolutionary relationships between the GGS isolates in these two collections.

Expression and characterisation of exofoliative toxin in Group A streptococcus

Group A streptococcus is a Gram-positive organism that is associated with a wide range of diseases in humans. These include pharyngitis, skin diseases and the post-infectious sequelae rheumatic fever and rheumatic heart disease. A wide number of virulence factors have been characterized in GAS. These include adhesins, factors that help the bacteria avoid host immune defenses and toxins.

Exfoliative Toxin (ET) is an important virulence factor in Staphylococcus that contributes to skin disease and bacterial dissemination. Our own studies have determined a gene encoding an ET homologue to be present in all GAS isolates. In this project we will characterize ET in GAS. The ET gene will be cloned into an expression vector for purification of ET and anti-ET antibodies produced in mice. These antibodies will be used in Western blots to investigate the expression of ET by multiple GAS isolates. Sequencing of the ET gene in these isolates will be undertaken to investigate the allelic diversity of the gene. Through homologous recombination we will also generate an ET deficient GAS strain. This strain will be compared to the parental host strain in a mouse infection model.

Molecular Cancer Epidemiology Laboratory
Dr Amanda Spurdle
Phone: 3362-0371
Email: Amanda.Spurdle@qimr.edu.au

Mutation analysis of high-risk cancer predisposition genes in endometrial cancer

A proportion of patients with endometrial cancer present with a family history of endometrial and other cancers. This proportion is likely to vary depending on how endometrial cancer cases were identified, especially for cases identified via a cancer clinic versus those recruited as incident cases in the general population.

We are conducting a study to establish which genes are mutated in endometrial cancer cases recruited in the general population. Analysis of tumour protein expression has been undertaken for proteins encoded by the known endometrial cancer predisposing mismatch repair (MMR) genes MLH1, MSH2 and MSH6.
Loss of protein expressions suggests the presence of a mutation in some cases, but genetic mutations in exonic regions have not been identified in all of these patients.

This project will involve investigation of regulatory regions of MMR genes for cancer-causing mutations in endometrial cancer patients. It will provide experience in gene alignment, primer design, sequencing, and outside of the protein-coding exons have yet to be screened. It will also provide experience in data mining, principally publication searches, required to identify methodologies commonly in use for mutation screening of such regulatory regions.

Timeline: 4-5 weeks, preferably over November/December 2008, but subject to discussion

Molecular Parasitology Laboratory
Dr Luke Moertel
Phone: 3362-0408
Email: Luke.Moertel@qimr.edu.au

Parasitic Worm Infection

Our laboratory researches the biology and epidemiology of parasitic worms of humans and we aim to develop new interventions and diagnostic procedures that will lead to their elimination.
We work on schistosomiasis and echinococcosis (hydatid disease), two major diseases caused by parasitic worms.

The schistosomiasis research has a field focus in China and we have the following projects suitable for Honours and PhD students:

• Epidemiological and human genetic studies to determine genetic factors associated with infection and disease
• Analysing the molecular and cellular mechanisms leading to formation of fibrotic hepatic lesions, the major contributing source of the chronic disease of schistosomiasis
• Using a gene microarray, that contains the majority of the schistosome transcriptome, along with protein arrays, proteomics analysis and laser capture microscopy to investigate differential gene expression during different stages of the schistosome lifecycle, strain variation and the effect of drugs and vaccines on schistosome worms.
• Studies on schistosome iron metabolism, dyneins, secreted enzymes and surface molecules, including and receptors, such as the insulin receptor, to determine their potential as novel targets for drugs and vaccines
.
• Assessment of vaccines in murine models and buffaloes in China
.

---

Potential applicants are invited to contact the listed supervisors directly for more information about projects of interest.
Dates during which the project would be undertaken are determined in consultation with the supervisor after the acceptance of an offer of a summer studentship from the Education Coordinator.

      Summer Studentship Application Form 08(pdf)

Applications should include:

• Application form
• a brief curriculum vitae
• a web transcript of your academic record
• the names of two referees familiar with your work
• your ranking of the summer vacation projects of interest in order of priority

Applications must quote QIMR reference  Summer 08/09  and be mailed to:

The Education Co-ordinator
Queensland Institute of Medical Research
Post Office Royal Brisbane Hospital
Herston 4029
Queensland

The closing date for applications is Friday, October 17th 2008.
Applicants will be advised of a positive outcome of their application as soon as possible after the deadline and no later than Nov 12th 2008.

Enquiries:

	Simone Cross
	Education Coordinator
	Email:education@qimr.edu.au
	

Back to Top