John Sled

Research Synopsis

Imaging technologies adapted to study experimental mice have a unique role in addressing current questions about the relationships between genes and disease. The sequencing of the human and mouse genomes in combination with the powerful genetic tools now available for the mouse have brought mice to the forefront as a means to understand development and model human disease. These genetic relationships, however, tend to be complex with genes having multiple roles and often complex interactions with other genetic and environmental factors. As with clinical practice, imaging technologies provide a means to examine in vivo the structure and function of whole organs or the whole mouse. This high level view allows one to find genotypephenotype relationships that are unexpected and allows one to examine questions about the patterning and structure of an organism that would not be apparent in a more focused molecular or cellular analysis.

At the Mouse Imaging Centre of the Hospital for Sick Children, we are using high resolution MRI, CT, ultrasound, and optical techniques to study mouse development and mouse models of disease. These imaging technologies provide three and four dimensional views of the structure and function of an organism and have been applied at the Centre to study mice modelling diverse disorders. Research at the Centre focuses on development of new imaging technologies for mice, development of analysis methods to aid the interpretation of the vast datasets that these technologies produce, and answering biological questions that can be uniquely addressed using imaging techniques.

One of several projects underway in my lab is a study of microvascular patterning in the placental circulation using microcomputed tomography. This goal of the work is to understand the relationships between the pattern of placental circulation, factors that modify this pattern, and the human condition intrauterine growth restriction (IUGR), which is normally characterized by abnormal placental vasculature. IUGR is one of the most serious disorders of pregnancy, resulting in perinatal death or premature birth of very low birth weight babies.

Another project is the use of high resolution MRI to detect subtle differences in brain morphology in mutated mice having abnormal behaviour. These structural findings are used to explain the observed effect of the mutation and to guide subsequent histological investigation. A related project underway is the development of functional MRI techniques for mouse to aid in localizing the brain regions affected by a mutation.

View our lab website for more information.

Recent Publications

• S. Kulandavelu, D. Qu, N. Sunn, J. Mu, M. Rennie, K. Whiteley, J. Walls, N.A. Bock, J. Sun, A. Covelli, J.G. Sled, S.L. Adamson. “Embryonic and Neonatal Phenotyping of Genetically Engineered Mice.” ILAR (In press), 2005.
• B.J. Nieman, A.M. Flenniken, R.M. Henkelman, J.G. Sled. “Anatomical Phenotyping in the Brain and Skull of Mutant Mice by Magnetic Resonance Imaging and Computer Tomography.” Physiological Genomics (In press), 2005. R.M. Henkelman, X.J. Chen, J.G. Sled. “Disease phenotyping: Structural and functional readouts.” In: Imaging in Drug Discovery and Early Clinical Trials. Ed. Marcus Rubin. Berlin: Birkhäuser Verlag, 2005.

Graduate Students

Tiffany Chien
Sarah Debebe
Anum Rahman
Anastasia Smolina