The Role of DNA Repair Proteins in Blood Cancers

Overview

Topic status: We're looking for students to study this topic.

This project focuses on analysis of the DNA damage response pathway in human cells. This DNA damage response pathway is a crucial component of the surveillance network that maintains stability and integrity of our genome. Maintenance of genomic stability is critical for cellular homeostasis, with genomic instability leading to cancer or cell death. The ATM-dependent DNA Damage Response Pathway is specific for alteration in chromatin induced by one particular form of DNA lesion, DNA double-strand breaks (DSBs), that may be caused by normal genomic transactions such as meiotic recombination and the maturation of the immune system genes via V(D)J recombination, the cell's own metabolic environment (e.g hydrolysis and oxidation of DNA by endogenously generated reactive oxygen), error prone internal machinery (e.g. replication fork collapse), or may be due to exogenous agents such as ionizing radiation (IR), and certain chemotherapeutic drug.

DNA repair pathways are vital in protecting cells from becoming cancerous. However, cancer cells adapt and alter these repair pathways to allow their rapid, un-checked cell growth. This project will study how specific repair proteins involved in the repair of DNA double strand breaks are controlled in blood cancers. We will analyse the expression of a number of DSB repair proteins in blood cancer cell lines and will utilise tissue microarray screens of blood cancers to determine what factors are up and down regulated. Included in these screens will be the hSSB1 and 2 genes, which were recently identified by our team (Richard et al., Nature, 2008). Our aim is to identify possible diagnostic and prognostic markers of blood cancers.

Hypothesis: Genomic stability is critical to prevent cancer, yet we know that cancer cells adapt the DNA repair and signaling machinery to allow their rapid un-checked cell growth. This same DNA repair machinery is also key to allowing the genetic variation within the tumor environment, which can accelerate cell growth and allow drug resistance to occur. Cancer cells can alter these pathways by changing the levels of specific protein components of the pathway. We hypothesise that blood cancers alter DSB repair pathways to allow rapid cellular growth.

Aim 1: Screen blood cancer cell lines to determine expression levels of key DSB protein
markers.

Aim 2: Screen tissue microarrays of blood cancers to determine protein expression levels and cellular characteristics

Aim 3: Analyse data to determine which markers have diagnostic prognostic potential

Methods that will be developed in the course of this project:

  • Cell culture, microscopy
  • SDS PAGE, immunoblot
  • TMA analysis
  • Data analysis
Study level
Honours
Supervisors
QUT External Dr Derek Richard (QIMR)
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Contact

Please contact the supervisor.