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Dr James Dachtler

2012 pump priming award recipient

Dr James Dachtler, Wellcome Trust Junior Investigator Development Fellow, University of Leeds

Autism and schizophrenia are chronic and severe conditions that have a relatively high prevalence within the population, and in part are thought to be caused by disruptions to a person’s genes. One family of genes that has gained recent attention are the neurexins. Despite this, little is known about how disruptions to the neurexin genes results in altered neurobehaviour and neuronal function.

While working with humans is problematic due to ethical and other confounding factors, mice with similar genetic disruptions are available. I have examined these mice and found they display behaviours similar to those found in autistic and schizophrenic patients. I am now in a position where the next stage of my research is to determine how these genetic disruptions caused the behaviours that I have observed.

The British Pharmacological IPF grant has enabled me to purchase the electrophysiological equipment that I require to launch a novel series of experiments.

My pilot data led me to hypothesise that neurexin disruptions may cause altered neuronal activity within a discrete brain region(s) or may prevent the correct neural signalling between multiple brain regions, but as yet, no one had explored this. The grant allowed me to directly test this hypothesis.

The pilot data generated from this work will be completely novel and has allowed me to compete for grant funding in the future to allow me to establish myself as an independent researcher. It is hoped that this work will discover new targets to treat the disabling phenotypes of autism and schizophrenia associated with these rare mutations.

Resulting papers:

  • Dachtler J, Glasper J, Cohen RN, Ivorra JL, Swiffen D, Jackson A, Harte MK, Rodgers RJ, Clapcote SJ (2014). Deletion of α-neurexin II results in autism-related behaviours in mice. Translational Psychiatry, 4:e484. 
  • Dachtler J, Ivorra JL, Rowland TE, Lever C, Rodgers RJ, Clapcote SJ (2015). Heterozygous deletion of α-neurexin I or α-neurexin II in mice results in behaviors relevant to autism and schizophrenia. Behavioral Neuroscience, 129 (6):765-776. 
  • Dachtler J, Elliott C, Rodgers RJ, Baillie G, Clapcote SJ (2016). Missense mutation in DISC1 C-terminal coiled-coil has GSK3β signaling and sex-dependent behavioral effects in mice. Scientific Reports, 6:18748.
The pump priming grant has been acknowledged in these manuscripts.