Ryan Cabot

 

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Research Program

Protocols have been developed over the past 40 years that enable us to produce mammalian embryos in the laboratory that can give rise to healthy, live-born animals. These advances enhance reproductive efficiency in domestic livestock; these advances impact both production agriculture and biomedicine. Despite the fact that high quality embryos that are capable of developing into healthy offspring can be produced in the laboratory, it is well-established that embryos produced in the laboratory (also called in vitro produced embryos) often show a reduced ability to undergo successful development as compared to embryos that are not housed in the laboratory. Specifically, in vitro produced embryos can possess aberrant gene expression, altered epigenetic states, and display perturbed patterns of fetal growth.

Although we understand that the early embryo must turn genes on and off at precise time points in order to secure successful development, we lack a detailed understanding of the mechanisms that allow this regulation to take place. Our long term goal is to understand how the cells of the early embryo are able to coordinate gene activation appropriately to give rise to developmentally competent embryos. This new knowledge will enable us to develop improved methods to address aspects of infertility.

One area we are currently exploring is the role that nuclear transport receptors serve in partitioning chromatin remodeling enzymes and transcription factors between the nucleus and the cytoplasm in mammalian oocytes and embryos. Our published data suggest that porcine embryos have differing developmental requirements for individual members of the karyopherin a family of nuclear transport receptors, enzymes that mediate the import of intracellular cargoes bearing nuclear localization signals (NLSs) into the nucleus.

Current projects are aimed at:

  1. Identifying the intracellular proteins transported by an oocyte-specific karyopherin a receptor, known as karyopherin a7.

  2. Determining the developmental requirements of karyopherin a receptors expressed during early embryo development.

  3. Determining the effects that in vitro embryo manipulation have on nuclear import mediated by the karyopherin a family of transport receptors.

The domestic pig is the primary research model used in our laboratory, and we use this model for the following reasons:

  1. The domestic pig is a species with worldwide agricultural importance. Through identifying ways to improve reproductive efficiency in this species we are able to contribute to global food security.

  2. The embryo of the domestic pig follows a timeline very similar to that of the human embryo for the first week of development. While this may seem like a very short timeframe when considering pregnancy lasts roughly 16 weeks in the pig and roughly 40 weeks in humans, fundamental events during the first week of development can profoundly impact development that takes place weeks later during pregnancy.

  3. Oocytes from the domestic pig and human (and consequently their embryos for the first week of development) are of nearly equal size. Rodent oocytes (and their embryos), while often used as a model for fundamental developmental events during embryo development, are only half the diameter of human oocytes. Being able to model events that human embryos may experience during a critical window of early development in a species that is of similar size allows us to test hypotheses in a physiologically relevant context.