Adam Hargreaves

Sir Henry Wellcome Fellow

 

Research Interests

The main theme of my research interests involves how changes in the genome and alterations in gene regulation can give rise to novel phenotypes, and how these relate to evolutionary adaptation. I have predominantly used 2nd generation sequencing and in silico analyses to explore these areas in venomous snakes. Snake venom presents itself as an ideal model due to its extensive variability, the importance of gene duplication in its diversification, and its fundamental importance as an evolutionary innovation in snakes. This research led to several highly significant insights, including casting doubt on the previously accepted hypothesis that venom evolved only once in reptilian evolution, and highlighting the role of gene duplication and subfunctionalisation (not "recruitment") in the origins of snake venom toxins.

I am also interested in genome evolution within rodents, and the effect genomic alterations have had on gene expression and adaptation to their environment (for example, living in a desert habitat). This has included the sequencing and analysis of the sand rat, a desert rodent and an experimental model for Type II diabetes. We have found a mutational hotspot within the genome of this animal, leading to unprecedented mutation in a number of functionally essential genes, including the Pdx1 homeobox gene.

My current project is funded by the Wellcome Trust and seeks to use the inhibitors venomous snakes use to protect themselves against their own venom to develop novel antivenoms. In particular I am focussed on developing a novel method of antivenom production which is cheap and requires no live animals.

 

Contacts

Email: adam.hargreaves@zoo.ox.ac.uk
 

Websites

 

Selected Publications

  • Hargreaves, A. D., Long, Z., Christensen, J., Marletaz, F., Liu, S., Li, F., Gildsig Jansen, P., Spiga, E., Thye Hansen, M., Vendelbo Horn Pedersen, S., Biswas. S., Serikawa. K., Fox, B., Taylor, W. R., Mulley, J. F., Zhang, G., Heller, R. S. and Holland P. W. H. (2017). Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster. PNAS. 114: 7677-7682.

  • Hargreaves, A. D. and Mulley, J. F. (2015). Assessing the utility of the Oxford Nanopore MinION for snake venom gland cDNA sequencing. PeerJ. 3:e1441

  • Hargreaves, A. D., Tucker, A. S. and Mulley, J. F. (2015). A critique of the Toxicoferan hypothesis. Evolution of venomous animals and their toxins

  • Hargreaves, A. D., Swain, M. T., Hegarty, M. J., Logan, D. W. and Mulley, J. F. (2014). Restriction and recruitment - gene duplication and the origin and evolution of snake venom toxins. Genome Biology and Evolution 6(8): 2088-2095

  • Hargreaves, A. D., Swain, M. T., Logan, D. W. and Mulley, J. F. (2014). Testing the Toxicofera: comparative reptile transcriptomics casts doubt on the single, early evolution of the reptile venom system. Toxicon 92: 140-156

  • Mulley, J. F., Hargreaves, A. D., Hegarty, M. J., Heller, R. S. and Swain, M. T. (2014). Transcriptomic analysis of the lesser spotted catshark (Scyliorhinus canicula) pancreas, liver and brain reveals molecular level conservation of vertebrate pancreas function. BMC Genomics 15: 1074

  • Hargreaves, A. D. and Mulley, J. F. (2014). A plea for standardized nomenclature of snake venom toxins. Toxicon. 90: 351-353

  • Harrison, R. A., Hargreaves, A., Wagstaff, S. C., Faragher, B. and Laloo, D. G. (2009). Snake envenoming: a disease of poverty. PLoS Neglected Tropical Diseases. 3(12): e569