Functional characterization of long non-coding RNA in melanoma and breast cancer cell lines

Project code:  MHS053

Department

Auckland Cancer Society Research Centre

Location

Auckland

RNAs were long thought to act mainly as carriers of genetic information between DNA and the protein-synthesising machinery of the cell. Recent whole genome sequencing technology has demonstrated that protein coding open reading frames comprise only about 1.2% of the human genome. On the other hand, 70-90% of the genome is transcribed as non-protein coding RNA (ncRNA). Initially regarded as ‘junk’, these transcripts have been found to possess many regulatory roles and represent a largely unexplored area of cell biology.

The best-known class of ncRNA comprises small regulatory RNAs called microRNAs, but recent studies have revealed that the transcriptome is replete with long ncRNAs (lncRNAs). The emerging role of lncRNAs in different aspects of biology provides encouragement for further studies on their roles in normal cell development and disease.

The major goal of this project is to investigate functional roles of selected candidate lncRNAs derived from melanoma and/or breast cancer cell lines. We will investigate the dynamic expression of candidate lncRNAs species. We will also manipulate the expression of these genes and investigate downstream targets as clues to the function of these candidates.

Skills

The project involves application of basic molecular biology techniques including mammalian cell culture, RNA and DNA extraction, cloning techniques, PCR and reverse transcription followed by PCR. These techniques will provide the candidate great basic skills required for performing experiments in molecular biology laboratories.

An In Silico study: can the modulation of miRNA expression through diet, impact cancer?

Project code:  MHS069

Department

Auckland Cancer Society Research Centre

Location

Auckland

Supervisor

Dr Karen Bishop

MiRNAs are small, non-coding RNAs that regulate gene expression. Bioactive compounds from foods can modulate miRNAs and thus influence gene expression. An in silico analysis of pathways will be used to speculate how food bioactives could be used to modify cancer risk and/or progression. This project would suit a student intending to progress to an Honours or Masters degree next semester, and other interested students are welcome to apply.

Skills

  • Critical review of the literature
  • Use of specialised software
  • Analysis of data
  • Presentation of findings
  • Preparation of a manuscript 

Halting the brain cancer incursion

Project code:  MHS074

Department

Auckland Cancer Society Research Centre

Location

Auckland

Supervisor

Dr. Sandy Chen

One of the key characteristics of cancer cells is their ability to invade and spread to adjacent and distal tissues, and this is usually associated with a poor clinical outcome. Identifying compounds that target this invasive phenotype is therefore of great interest in anticancer drug development.

Brain cancers are often highly invasive, however, current approved therapy do not target this particular characteristic. This project aims to evaluate the effect of a novel anticancer agent targeting cancer cell invasion in NZ brain cancer cell lines.

Skills

  • Analysis of in vitro cancer cell invasion in a 3-dimensional extracellular matrix model: this project will involve the development and application of a method for analysing images of cancer cell invasion in a 3-D matrix.
  • Statistical analysis.
  • Literature review.
  • Oral presentation.

An investigation into the possible applications of the Zika and related family of viruses in anticancer therapy

Project code:  MHS111

Department

Auckland Cancer Society Research Centre

Location

Auckland

Supervisor

Dr. Sandy Chen

The mosquito-borne Zika virus was first identified in the 1940s and is currently at the centre of media attention. This is due to recent outbreaks in the Americas and the identification of a link between maternal infection and the development of microcephaly in newborns. Neuroprogenitor cells (immature 'stem' cells from the brain) have been found to be specifically targeted by the Zika virus and is thought to be reason for the development of foetal brain abnormalities.

Virus-directed therapy is a niche area in anticancer research, which promises a more cancer-targeted mode of action. It has been used in evoking an immune cancer-targeted response as well as in the delivery of cancer-targeted drugs. However, the possibility of a Zika or related family (Flaviviridae) application in anticancer therapy has not been explored.

Glioblastoma is the most prevalent form of adult brain cancers, which is hypothesised to be initiated and/or promoted by the presence of immature neuroprogenitor cells. This project aims to explore the possibility of using the Flavivirus family as a tool for brain cancer-directed therapy.

Skills

  • Critical analysis of the literature.
  • Oral presentation.
  • Process of preparing a manuscript for publication.
  • Using a reference management software.

Assessing importance of the serum Aldo-keto reductase activity levels in high-risk prostate cancer

Project code:  MHS117

Department

Auckland Cancer Society Research Centre

Location

Auckland

Supervisor

Nishi Karunasinghe

Aldo-keto reductase 1C3 is an enzyme with multiple substrates including that of the steroidal pathway. It is involved in the conversion of testosterone from androstenedione and dihydrotestosterone from androstanedione, and adrenal derived dehydroepiandrosterone to androstenidiol. Besides AKR1C3 is involved in conversion of the prostaglandin D2 series to PG F2α, and 11β-PGF2α while the reducing the J series prostaglandins that are important in cell differentiation. This enzyme is also known for its action in metabolising polycyclic aromatic hydrocarbons.

Increased expression of the AKR1C3 gene is reported from advancing prostate cancer. Meanwhile, work from our laboratory have shown a negative association of G allele of the AKR1C3 rs12529 single nucleotide polymorphism  with serum prostate specific antigen level as well as positive adverse events with androgen deprivation therapies. However, it is not yet certain whether these variations are associated with activity of the AKR1C3 enzyme level.

The proposed project intends to measure the AKR1C3 activity level in serum samples of prostate cancer patients and controls, and to correlate these to the genotype of interest.

Skills

1. Handling of biological fluids

2. Spectrophotometric analyses

3. Statistical methods

Genetic variation in histopathology data of prostate cancer patients’ undergone prostatectomy

Project code:  MHS118

Department

Auckland Cancer Society Research Centre

Location

Auckland

Supervisor

Nishi Karunasinghe

Our studies indicate that there are variations in steroidal hormone levels associated with genetic polymorphisms of steroidal pathway genes. We wish to assess whether such variations affect prostate cancer histopathology as well. Therefore, we wish to extract details of histopathology data from the LabPlus records for 206 prostate cancer patients undergone prostatectomy and have given consent to accessing such data.(Data extraction protocol is approved by the Ethics- ref NTY/05/06/037/AM09). Such data will be finally assessed against available genotype data for these patients. The purpose of such studies is to find out whether patients can be stratified based on their genotype for better management options for post-surgery events. Data to be retrieved from the LabPlus database include-

(a) prostate weight

(b) tumor volume and weight

(c ) tumor location

(d) post-surgery Gleason score

(e) positive extracapsular extension or seminal vesicle invasion

(f) Lymph node status

(g) perineural invasion status

Skills

1. Understanding confidentiality when dealing with patient data.

2. Getting experienced with Concerto/Éclair to extract patient data

3. Statistical analysis skills

4. Reporting skills

Herbs from Pacific to battle colorectal cancer

Project code:  MHS123

Department

Auckland Cancer Society Research Centre

Location

Auckland

The traditional Māori diet followed a very different pattern to the current eating habits. This is increasingly being recognized as the reason for increasing burden particularly of colorectal cancers among Māori. In the early 2000s, the comparative rates of adenomas among New Zealand Europeans and Māori were 16.7% and 8.7% respectively. However, National Cancer Statistics indicate that more recently this gap has closed, with New Zealand Europeans recording an age standardized colorectal cancer rate of 42.8 per 100,000 compared to 33.3 per 100,000 among New Zealand Māori and both producing similar death rates due to colorectal cancer.

Herbs that have been traditionally used by Māori could be carrying health benefits that could compete with the negative effects of western diets. Some such herbs have been used commonly in the Pacific region. Therefore, we wish to carry out a review of scientific proof of such traditional plants that have been recorded from the Pacific including that from New Zealand.

If sufficient evidence is collected, this study can potentially continue to a masters project.

Skills

Literature searching, critical evaluation and data analysis.

Enhancing endoplasmic reticulum stress to target cancer

Project code:  MHS133

Department

Auckland Cancer Society Research Centre

Location

Auckland

Supervisor

Dr Dean Singleton

Certain cancer types are highly secretory and this results in elevated levels of endoplasmic reticulum (ER) stress. We have identified small molecule methyltransferase inhibitors that cause ER stress in cells. This project will investigate how this ER stress occurs and will determine whether these methyltransferase inhibitors are selectively toxic to secretory cancer cells including multiple myeloma, breast and pancreatic cancer cell lines.  

We are looking to recruit students with a passion for cancer research and drug development and interest in pursuing postgraduate studies.

Skills

This project will involve:

  • Cell culture
  • Cytotoxicity assays
  • Western immunoblotting
  • RT-qPCR
  • Immunofluorescent staining and microscopy