Analysis of a mouse model of longevity

Description of projects available to graduate students:
Immunity is a determinant of survival and individual fitness. Hence, we are interested in examining the immunologic basis of longevity or lifespan extension.

We have recently published about a mouse model that has ~40% extension in lifespan, is cancer resistant, and has retained thymic architecture even in its extreme old age. The thymus normally involutes with aging, its loss has been argued to contribute to age-related decline of antigen-specific immunity.

Our mouse strain is deficient in PAPPA (pregnancy-associated plasma protein A), the enzyme regulate the availability of bioactive IGF (insulin-like growth factor) for signaling in tissues by degrading inhibitory IGF-binding proteins. PAPPA-KO mice have normal IGF, insulin, and glucose levels

Projects are therefore designed to:
(a) examine mechanism(s) of thymic preservation, of interest is whether thymic preservation is controlled by pathway(s) distinct from normal age-related thymic involution;
(b) examine the impact of thymic preservation on innate and adaptive immune functions across the lifespan;
(c) distinguish between PAPPA (IGF)-dependent and immune-dependent mechanisms of cancer resistance;
(d) examine PAPPA(IGF) - immune interactions in the regulation of lifespan.

Techniques graduate student will learn:
Genetic typing and genetic crosses of mice strains
Cell/Tissue culture
Flow cytometry
Multiplex quantitative PCR
Multiplex cytokine/humoral assays
Bioassays of immune function
Adaptive transfer of immune cells from one mouse to another
Cell imaging
Gene expression assays including miRNA arrays