Using non-invasive in vivo imaging to address the 3Rs in high-throughput mouse phenotyping

In the wake of the first draft of the full mouse genome sequence, large-scale mutagenesis programmes are underway that will produce mice with gene knockouts/point mutations for each of the approximately 25,000 genes in the mouse genome. Analysis of these mice in coming years will give new insights into the genetic basis of human disease and biology, as novel genes are identified that impact upon mammalian physiology and morphology. This studentship will develop non-invasive imaging of live mice to reduce the numbers of mice generated in high-throughput mutagenesis programs and start to refine experimental strategies for working with mouse models. We will use non-invasive in-vivo magnetic resonance imaging (MRI), to assess if this imaging technology can help us understand the function of genes within the brain, which will enable us remove major "bottlenecks" in the development of new diagnosis tests for genetic disease and human gene therapies.

Colgan N, Siow B, O'Callaghan JM, Harrison IF, Wells JA, Holmes HE, Ismail O, Richardson S, Alexander DC, Collins EC, Fisher EM, Johnson R, Schwarz AJ, Ahmed Z, O'Neill MJ, Murray TK, Zhang H, Lythgoe MF (2016). Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease. Neuroimage 125:739-44. doi: 10.1016/j.neuroimage.2015.10.043

Holmes HE, Colgan N, Ismail O, Ma D, Powell NM, O'Callaghan JM, Harrison IF, Johnson RA, Murray TK, Ahmed Z, Heggenes M, Fisher A, Cardoso MJ, Modat M, Walker-Samuel S, Fisher EM, Ourselin S, O'Neill MJ, Wells JA, Collins EC, Lythgoe MF (2016). Imaging the accumulation and suppression of tau pathology using multiparametric MRI. Neurobiology of Aging 39:184-94. doi: 10.1016/j.neurobiolaging.2015.12.001

Wells JA, O'Callaghan JM, Holmes HE, Powell NM, Johnson RA, Siow B, Torrealdea F, Ismail O, Walker-Samuel S, Golay X, Rega M, Richardson S, Modat M, Cardoso MJ, Ourselin S, Schwarz AJ, Ahmed Z, Murray TK, O'Neill MJ, Collins EC, Colgan N, Lythgoe MF (2015).  In vivo imaging of tau pathology using multi-parametric quantitative MRI.  NeuroImage 111:369-78. doi: 10.1016/j.neuroimage.2015.02.023

Wells JA, Holmes HE, O'Callaghan JM, Colgan N, Ismail O, Fisher EM, Siow B, Murray TK, Schwarz AJ, O'Neill MJ, Collins EC, Lythgoe MF (2015).  Increased cerebral vascular reactivity in the tau expressing rTg4510 mouse: evidence against the role of tau pathology to impair vascular health in Alzheimer's disease.  Journal of Cerebral Blood Flow and Metabolism 35(3):359-62. doi: 10.1038/jcbfm.2014.224

O'Callaghan J, Wells J, Richardson S, Holmes H, Yu Y, Walker-Samuel S, Siow B, Lythgoe MF (2014).  Is your system calibrated? MRI gradient system calibration for pre-clinical, high-resolution imaging.  PLoS One 9(5):e96568. doi: 10.1371/journal.pone.0096568

Ma D, Cardoso MJ, Modat M, Powell N, Wells J, Holmes H, Wiseman F, Tybulewicz V, Fisher E, Lythgoe MF, Ourselin S (2014).  Automatic structural parcellation of mouse brain MRI using multi-atlas label fusion.  PLoS One 9(1):e86576. doi: 10.1371/journal.pone.0086576

 

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PhD Studentship

Grant reference number

NC/K500276/1

Award date:

Sep 2011 - Sep 2015

Grant amount

£120,000

Primary 'R'

Reduction

Scientific Discipline

Cells and systems
Genetics

Technologies/approach

Imaging

Keywords

MRI