Biotechnology can be broadly defined as ‘the use of biological processes to solve problems or make useful products’, and has been practiced by human societies since the beginning of recorded history - in activities such as baking bread, brewing alcoholic drinks and the selective breeding of plants and animals. Modern biotechnology involves precisely modifying the genome of an organism to alter its phenotype for a defined purpose.
Our group is interested in biomedical applications of animal biotechnology. Recent decades have seen a vast increase in our understanding of the genetic basis of many diseases. This is largely due to DNA sequence information coupled with powerful methods of genetic engineering, principally in mice. Mice are however often of limited value in translating basic knowledge into clinical advances, such as preclinical evaluation of new medical techniques. Large animals, notably pigs, can be very useful for research closer to the clinic, being similar in size and anatomically and physiologically closer to humans. We believe that genetically-modified pigs can provide powerful new resources to improve the understanding, diagnosis and treatment of serious disease conditions.
Tools for genetic engineering are continually being developed and refined, and we are extending new methods to livestock. Technologies used in our laboratories include: transfer vectors for large and multiple transgenes, site-specific recombination for conditional gene expression, adeno-associated viral vectors for local gene activation, manipulation of porcine oocytes and early embryos, streamlined gene targeting using RNA-guided endonucleases, and laser-guided tissue microdissection for precision transcriptome analysis.
Porcine disease models
This section, led by Dr Tatiana Flisikowska, is pursuing the generation and characterisation of porcine models of human colorectal cancer, osteosarcoma, pancreatic ductal adenocarcinoma, and also cardiovascular diseases.
Genetic and epigenetic analysis
The section led by Dr Krzysztof Flisikowski is using genetic and epigenetic analyses to understand the aetiology and progression of porcine colorectal cancer, pancreatic ductal adenocarcinoma and osteosarcoma and determine how closely porcine models resemble the human disease.
The xenotransplantation section, led by Dr Konrad Fischer, is part of an ongoing national consortium entitled "Biology of xenogeneic cell, tissue and organ transplantation – from bench to bedside” and has the remit of developing genetically multi-modified donor pigs to overcome immune rejection of pig-to-primate xenografts and improve their functional properties.
- Gene editing directly in rabbit embryos using zinc finger nucleases
- Analysis of a spontaneous mutation causing stillbirth in cattle
- Gene targeted modification of the tumour suppressor p53 in pigs
- Pig model of human inherited predisposition to colorectal cancer
- Fluorescent reporter pigs for conditional gene expression
- Pigs with conditionally expressed oncogenic KRAS
- A porcine model of osteosarcoma
- Multi-modified pigs for xenotransplantation
- Transgene stacking: sequential placement of xenoprotective transgenes
- Review: Genetically engineered pigs as models for human disease
- Review: Assembling multiple transgenes for xenotransplantation