Audit of deaths from Motor Neuron Disease in NZ

Project code:  MHS003

Department

Pharmacology and Clinical Pharmacology

Location

Auckland

Supervisor

Emma Scotter

Background

Motor Neuron Disease is a fatal and incurable movement disorder. This disorder is characterised by death of upper and lower motor neurons within the brain and spinal cord, causing progressive loss of movement function. There is a wide range of genetic risk factors for motor neuron disease, as well as geographic ‘hotspots’ of increased disease incidence suggestive of environmental contributors. Motor Neuron Disease is presumed to affect ~1 in 15,000 New Zealanders, based on international incidence figures, but no studies have comprehensively examined MND incidence in NZ. 

This study aims to audit the incidence of Motor Neuron Disease in NZ over time. The audit will inform the possible inclusion of NZ Motor Neuron Disease patients in an Australasian-wide registry. 

Specific objectives include:

-Conduct a literature review

-Assist with sourcing data

-Conduct data analyses

-Prepare a report on findings including graphs and statistical analyses

-Assist with writing for publication (co-authorship) 

Skills

-Designing research questions

-Working with and managing large data sets

-Scientific writing

-Software: Microsoft Excel, statistical and graphing software

The student will be based at the Centre for Brain Research, University of Auckland.

Good riddance to bad rubbish: waste disposal in Motor Neuron Disease

Project code:  MHS004

Department

Pharmacology and Clinical Pharmacology

Location

Auckland

Supervisor

Emma Scotter

Background

Motor neuron disease is a fatal and incurable movement disorder affecting ~1 in 15,000 New Zealanders. This disorder is characterised by death of upper and lower motor neurons within the brain and spinal cord, causing progressive loss of movement function. The vast majority of motor neuron disease cases exhibit intracellular accumulation of a protein called TDP-43 in dying motor neurons. Intracellular TDP-43 accumulation is caused by a deficit in the ability of cells to clear waste (ie. degrade damaged proteins).

This study aims to use fluorescence proteins as biological “timers” to measure rates of protein degradation in the context of motor neuron disease.

Skills

-Mammalian cell culture

-Live cell imaging

-Image analysis

-Scientific writing

The student will be based at the Centre for Brain Research, University of Auckland. 

This pilot project is part of a larger program of research and there is potential for a successful candidate to continue into a Masters or PhD project.

Characterising synthetic cannabinoids

Project code:  MHS046

Department

Pharmacology and Clinical Pharmacology

Location

Auckland

Supervisor

Michelle Glass

Synthetic cannabinoids are a growing class of recreational drugs.  We have an ongoing collaboration with Stanford University to characterise a range of novel compounds and metabolites in order to understand the mechanism of action of drugs currently appearing in black market.  This project will involve receptor binding and functional assays on a range of compounds.

Skills

mammalian cell culture

Radioligand binding assays

cAMP functional assays

Investigation of factors that influence the integrity of the blood brain barrier endothelium during neuroinflammation

Project code:   MHS112

Department

  • Pharmacology and Clinical Pharmacology
  • Anatomy and Medical Imaging

Location

Auckland

Supervisor

Dr E Scott Graham

We have on offer an exciting summer project for a student interested in neuroinflammation particularly focused on the role of the blood brain barrier (BBB) microvascular endothelial cells.  We have developed a robust in vitro human BBB model [1, 2] which you will use to investigate how various inflammatory mediators disrupt BBB endothelial integrity, whereas others cause strengthening of the barrier. The project will be jointly supervised by Dr Scott Graham (Pharmacology Department) and Dr Simon O’Carroll (Anatomy Department) and the project will be based in the Centre for Brain Research labs in the School of Medical Sciences (FMHS).  We are particularly interested in expressions of interest from students who have a desire to conduct research at either honours or masters levels, or as part of their medical training. We have developed a world class research platform encompassing our ECIS [1, 2] and xCELLIgence technology [3] and other neuroinflammation resources [3-5].  So if you would like to join our team and have an interesting and challenging summer, then this could be for you!

Dr E Scott Graham
Dr Simon O’Carroll   


For some of our recent publications have a look at
1. Wiltshire, R., et al., Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors. Sci Rep, 2016. 6: p. 19814.
2. O'Carroll, S., et al., Pro-inflammatory TNF and IL-1 differentially regulate the inflammatory phenotype of brain microvascular endothelial cells Journal of Neuroinflammation, 2015.
3. Kho, D., et al., Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time. Biosensors (Basel), 2015. 5(2): p. 199-222.
4. MacDonald, C., C.P. Unsworth, and E.S. Graham, Enrichment of differentiated hNT neurons and subsequent analysis using flow-cytometry and xCELLigence sensing. J Neurosci Methods, 2014. 227: p. 47-56.
5. van Kralingen, C., et al., Exposure to inflammatory cytokines IL-1beta and TNFalpha induces compromise and death of astrocytes; implications for chronic neuroinflammation. PLoS One, 2013. 8(12): p. e84269.

Skills

Skills you will experience during the summer project include cell culture, ECIS technology (barrier integrity), xCELLigence technology (barrier integrity and cell viability) and the measurement of pro-inflammatory cytokine secretion using flow cytometry assays. See our recent publications for more detail on each of these methods and skills.

Exploring the relationship between cytisine, cotinine and craving for cigarettes

Project code:   MHS131

Department

Pharmacology and Clinical Pharmacology

Location

Auckland

Supervisor

A/P Malcolm Tingle

Around 5,000 deaths per annum in New Zealand are associated with tobacco smoking and second hand smoke exposure. Cytisine is a smoking cessation agent which has been used in Eastern Europe for decades, but it is not currently licenced for use in New Zealand. We have been studying cytisine in our lab, and have recently published the first paper on cytisine pharmacokinetics in humans. The next stage of the work is to look at pharmacokinetic/pharmacodynamics relationships.

Using previously collected data, the aim of this study is to explore whether the relationship between cytisine plasma concentration and craving for cigarettes is mediated by the amount of nicotine in a person’s body. 

Skills

This project is suitable for a BPharm student

  • Use of HPLC and LC-MS to measure plasma samples of cytisine and cotinine
  • Interpretation of data from human smokers about craving for cigarettes
  • Statistical analyses of the data