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Research interests

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The question at the centre of our research is how two gametes - sperm and egg - transform into an embryo when they combine in mammalian fertilisation: the gamete-to-embryo transition.  This is a fundamental process with major implications for the regulation of cellular potency and broad translational potential in the areas of infertility and stem cell biology.  We integrate embryological and molecular approaches developed by us in a mouse model.  Using piezo-actuated micromanipulation, we can achieve high rates of transgenesis via a method we developed (published in Science), generate offspring from 'dead' sperm and perform nuclear transfer cloning; at Bath, we produced England's first cloned mouse; indeed, this was the first adult to be cloned from an adult cell in any species (<http://www.egg2embryo.com/>).  Recently, we demonstrated the birth of offspring via a distinctive epigenetic pathway when sperm are injected into parthenogenetic embryos.  This finding overturns a centuries-old dogma established by Karl Ernst von Baer that animals develop from eggs and challenges the model of lineage specification proposed by twentieth century biologist, Conrad Waddington ('Waddington's Canal').  Our analytical methods include fluorescence imaging and sub-cellular transcriptomics.  We are developing next-generation genome editing, nanobiology and stem cell approaches and hold that regenerative medicine will remain impracticable without a thorough mechanistic understanding of the establishment of totipotency during the gamete-to-embryo transition.




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