Investigating novel gene function in neurodegeneration and behaviour
Stress response mechanisms in neurodegeneration
Neurodegenerative disease is becoming an increasing burden on healthcare and there is a continuing need to understand the cellular mechanisms involved and generate new therapeutic approaches. One important question to address is why distinct populations of neurons are vulnerable in these disorders despite widespread expression of the proteins involved. In recent years there has been a particular focus on the role of reactive oxygen species as factors that mediate the differential susceptibility of neurons. Indeed, oxidative stress and mitochondrial dysfunction have been implicated in all major neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Parkinson’s and Alzheimer’s disease. Furthermore, several pathogenic mutations in proteins that feature prominently in antioxidant pathways have been described in these disorders. Therefore, identification of pathways that counteract oxidative damage may identify new therapeutic strategies that are widely applicable to human disease.
As part of my research in the MRC Functional Genomics Unit, I identified the importance of the mitochondrial oxidation resistance 1 (Oxr1) gene for neuronal survival; loss of Oxr1 causes neurodegeneration in mice, whereas over-expression in vitro is able to confer protection against oxidative stress. Deregulation of this protein is also observed in human ALS and additional mouse models of neurodegeneration. Despite the apparent high level of evolutionary conservation of Oxr1-related proteins, virtually nothing is known about their role in vivo. My current research program aims to understand the function of this family of proteins using both neuronal cell culture, mouse models of disease as well as human induced pluripotent stem cells (iPSCs).
Gene x environment interactions in mental health
As well as a well-documented genetic component to human psychiatric disorders such as schizophrenia, both pre- and post-natal environmental factors play a significant role. How this ‘gene x environment’ interaction takes place is still unclear; however, work in mouse models is beginning to examine this phenomenon in more detail. I have a long-standing interest in this area, as well as studying the role of sleep and circadian rhythms as an important feature of psychiatric disease. I collaborate with groups within the University that study mouse mutants representing known pathways disrupted in schizophrenia and investigate how non-genetic factors can influence brain function and behaviour.
We are a new but well-funded group based in the Oxford Centre for Gene Function, equipped with the latest tools for mammalian molecular genetics and cell biology.
Those interested in discussing student projects or Fellowships please get in touch.
European Research Council
Motor Neuron Disease Association
Oxford Brain@McGill Neuroscience Partnership
Medical Research Council
Post-doctoral position (3-year MRC Career Development Fellowship) is currently being advertised in the group as part of a new programme of work with MRC Harwell. For more details see:
PhD studentships - October 2017 entry are currently being advertised for a potential project in the Oliver group at MRC Harwell. For more details see:
Peter has been awarded an MRC Programme Grant to continue studying the molecular function of the TLDc family of proteins using a combination of mouse genetics and cell biology. Advertisements for new post-doc positions will be released in January 2017.
Welcome to Julia Grasegger and Joery den Hoed who are joining the group this month and later this year for research placements
Science animation project Silent Signal is released - including collaboration between Peter Oliver and animator Ellie Land called 'Sleepless'
for more information see: http://www.silentsignal.org/
or watch the animation here: http://www.silentsignal.org/Collaborations/sleepless/
New paper from the group examining the function of Oxr1 in mitochondria is in press:
New paper from the group identifying the detailed transcriptional profile of the suprachiasmatic nucleus by RNAseq for the first time is in press in eLife:
Congratulations to Mattea Finelli in the group has been awarded the Johnson & Johnson Innovation Junior Research Fellowship at St Edmund Hall