This project aims to determine which proteins regulate inflammation, tissue regeneration in response to injury and cancer development and will play a crucial role in developing target-specific drugs.
Rationale
The major goal of this project is to investigate the role of poly-ADP ribose polymerase (abbreviated as PARP), an enzyme found in human cells, in the development of cancer and chronic inflammation. Our earlier research showed that the PARP protein is prevalent in human malignancies and that blocking it prevents tumour growth in mice. This project aims to elucidate the mechanism underlying this and pinpoint any additional crucial proteins that might be involved. The creation of PARP-deficient mice makes this project innovative and will boost existing studies.
Plan of work
We want to utilise cancer-causing chemicals to create inflammation and tumours in mice, which we'll then treat with several medications that inhibit PARP proteins. The use of gene-deficient mice, such as PARP-deficient mice, along with these medications is thought to reduce tumour burden. By analysing the tissue from these animals in the lab, we can learn what factors are responsible for this reduction. This research will help identify targets that might be involved in tumour suppression.
Animal welfare
Mice will be regularly observed for signs of discomfort and will receive any required treatment to ease that discomfort. Experience has demonstrated that mice can endure the procedures to be used in this protocol.
Three Rs
Replacement
The body’s response to cancer development is complex, involving cells and processes throughout the body. Currently, it is impossible to replicate these complexities in laboratory experiments; animal studies are necessary if new therapies are to be developed.
Reduction
The number of mice used in experiments has been calculated to maximise the amount of data produced per animal. The number of studies conducted will be decreased by comparing multiple treatment groups against a single control group. Multiple analyses of the tissues that have been taken by a single animal can maximise data collection while minimising the number of animals needed. We expect to use approximately 4,000 mice over five years.
Refinement
Following previous work, we have increased the monitoring of animals and improved techniques throughout to minimise any adverse effects and ensure that most of the animals will not exceed a ‘moderate’ degree of animal suffering. By refining our procedure, it is therefore expected that only 30% of all mice used will achieve a moderate degree of animal suffering.