Science & Publications

Previous projects

Building better models to uncover new targets and treatments

Our team develops a wide range of genetically engineered mouse and cell line models, from knockouts and point mutations to protein tagging, conditional and inducible expression, and humanised systems. Alongside building novel models, we run end-to-end preclinical studies in neurological, autoimmune, and tumour disease models. These capabilities allow us to investigate gene function, validate therapeutic targets, and test both small molecule and genetic therapies. We also enhance existing transgenic lines with new alterations and design controllable systems for gene up- and down-regulation. Explore some of our projects below.

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Publications

Factor VIII clotting factor knockout model

A CRISPR/Cas9-mediated knockout of Factor 8 clotting factor was generated as a mouse model of hemophilia A, developing spontaneous bleeds in the joints and arthropathy.

Antisense oligonucleotide administration to dystrophic mdx23 mouse model

The Duchenne muscular dystrophy mouse model, mdx23, was employed to examine if behavioural improvements could be achieved by repeated antisense oligonucleotide delivery via the cisterna magna.

Conditional bicistronic DUOX2 expression in neutrophils

A novel conditional bicistronic Duoxa2-Duox2 model was generated to investigate links between neutrophil reprogramming in the intestine and reactive oxygen species production by DUOX2, and expand the understanding of neutrophil plasticity due to the local environment.

Molecular maker of sperm cell health

Using human male semen samples, RAGE expression was identified as a molecular maker of sperm cell health. This target may be used to improve assisted reproduction through the removal of RAGE expressing sperm and facilitate in the diagnoses of unexplained infertility through its use as a biomarker of male infertility.

Duchenne Muscular dystrophy mouse models

Duchenne muscular dystrophy (DMD) brain comorbidities, which can have a severe impact on quality of life for patients, depend on mutation location in the dystrophin gene. Two DMD mouse models, mdx5cv and mdx52 were established to investigate the differing behavioural phenotypes.

Exon 53 skipping in Duchenne Muscular dystrophy mouse model

Exon skipping as a gene therapy in Duchenne’s muscular dystrophy has shown promising results in treating the muscular atrophy DMD. No current therapies address the brain abnormalities. A number of antisense oligonucleotide sequences were examined for their ability to induce exon skipping of exon 53 in the brain of the mdx52 dystrophic mouse model.

Brain delivery routes for ASOs in Duchenne Muscular dystrophy mouse model

Antisense oligonucleotide biodistribution and exon skipping were investigated by delivery via multiple routes to the brain – intracerebroventricular slow bolus and repeated via cannula, and intracisternal magna.

Compound investigation in Murine experimental autoimmune encephalomyelitis

The post-translational tRNA modification queuine tRNA ribosyltransferase (QTRT) has recently been identified as a novel target pathway in the treatment of a chronic multiple sclerosis model: murine experimental autoimmune encephalomyelitis (EAE). A library of queuine analogues were evaluated in the EAE model, identifying a number of active compounds.

Sarm1 knockout and epitope tagged mouse model

Sarm1 has been proposed to have roles in both innate immunity and neuronal degeneration. Novel CRISPR/Cas9-mediated SARM1 knockout and epitope tagged mice were generated to reveal that SARM1 does not regulate nuclear transcription, but is expressed in macrophages.

Dendritic cell specificity of Pellino2

Integration of epitope tag via CRISPR/Cas9-mediated homology-directed repair allowed expression of functional Pellino2 and detection of it’s dendritic cell specificity.

Humanised CD1a mouse model

CRISPR/Cas9-mediated homology-directed integration validated the Hipp11 intergenic region as a highly amenable mouse target for functional transgene insertion. It supported faithful, inducible expression of the full human CD1A gene, including promoter, coding, and non-coding regions, in macrophage and dendritic cells.