Dr James Hodge

Lab Overview

We are interested in how neural circuit activity underlies behaviour including circadian rhythms, sleep, memory and movement. We study these using Drosophila, molecular genetics, electrophysiology and optogenetics. We study the fundamental biology of behaviour and how they are affected by ageing, drugs and diseases including Alzheimer’s, Parkinson’s, Down’s, schizophrenia and neuropathies. We also studying the effect of neonicotinoid insecticides on fly and bee circadian rhythms and sleep.

Research Questions

1) Circadian rhythms and clock neuron excitability. How does light and temperature entrain the clock? How is time of day information communicated through the clock? What is the role of neuronal activity in circadian rhythms? What are the components of the membrane clock and how do they interact with the molecular clock?

2) Sleep and electrical activity in the brain. How is sleep regulated by circuits in the brain? What is the role of synaptic transmission and homeostasis in sleep? Which ion channels and receptors mediate sleep neuron electrophysiology and regulate sleep? Can sleep be artificially enhanced or suppressed?

3) How is neuronal excitability, circadian rhythms, sleep, memory and movement affected by ageing, drugs and diseases such as Alzheimer’s, Parkinson’s, Down’s and schizophrenia. Can novel mechanisms be identified and lead to new drugs?

4) What effects do insecticides have on insect neuronal excitability, circadian rhythms, sleep, memory and movement. 

Techniques

1) Electrophysiology. Whole cell current- and voltage-clamp of defined neurons recorded in the whole brain or in vivo. Synaptic recordings to measure transmission and plasticity. Measurement of spontaneous vesicular transmitter and evoked release, short-term depression and paired pulse recordings.  

2) Optogenetics. Electrophysiology and behavioural characterisation of large range of different optogenetic and thermogenetic activators and inactivators. GCaMP6f and membrane potential reporters.

3) Behaviour. Drosophila activity monitors, Drosophila arousal tracking system and for bees, Bee activity monitors, RFID monitoring of bees. Olfactory shock or sugar conditioning assay for adults and larvae. Judgement bias task. Locomotor assays for adults and larvae. Longevity assays.

4) Imaging. Confocal imaging, neurodegeneration assay for eye and central neurons.

5) Genetics. Forward and reverse genetics. Full range of promoter systems including inducible. CRISPR/Cas9 genome editing.

6) Molecular biology. Westerns, DNA gels, PCR and qRT-PCR.

7) Mathematical modelling. Dynamic clamp, Hodgkin-Huxley models of neurons and small network models.

Impact

We are collaborating with clinicians and industry to test new drugs for neurodegenerative disease. We perform regular internships with policy makers and industry. We support schools and BBC4 Christmas lectures perform Drosophila experiments. We deliver wide ranging public engagement talks, music and fly demonstrations at open days, Festival of neuroscience, Pint of science and with Guerrilla Science at the Eden Project, Secret Garden Party, Boomtown and Shambala festivals, Royal Shakespeare Company and Science Museum Late.

Selected Publications

Neonicotinoids disrupt memory, circadian behaviour and sleep.

Tasman K, Hidalgo S, Zhu B, Rands SA, Hodge JJL.Sci Rep. 2021 Jan 21;11(1):2061. doi: 10.1038/s41598-021-81548-2.PMID: 33479461 
 

Impaired Pre-Motor Circuit Activity and Movement in a Drosophila Model of KCNMA1-Linked Dyskinesia.

Kratschmer P, Lowe SA, Buhl E, Chen KF, Kullmann DM, Pittman A, Hodge JJL, Jepson JEC.Mov Disord. 2021 Jan 15. doi: 10.1002/mds.28479. Online ahead of print.PMID: 33449381
 

The Neonicotinoid Insecticide Imidacloprid Disrupts Bumblebee Foraging Rhythms and Sleep.

Tasman K, Rands SA, Hodge JJL.iScience. 2020 Nov 20;23(12):101827. doi: 10.1016/j.isci.2020.101827. eCollection 2020 Dec 18.PMID: 33305183 
 

Shaw and Shal voltage-gated potassium channels mediate circadian changes in Drosophila clock neuron excitability.

Smith P, Buhl E, Tsaneva-Atanasova K, Hodge JJL.J Physiol. 2019 Dec;597(23):5707-5722. doi: 10.1113/JP278826. Epub 2019 Nov 13.PMID: 31612994
 

Restoration of Olfactory Memory in Drosophila Overexpressing Human Alzheimer's Disease Associated Tau by Manipulation of L-Type Ca2+ Channels.

Higham JP, Hidalgo S, Buhl E, Hodge JJL.Front Cell Neurosci. 2019 Sep 10;13:409. doi: 10.3389/fncel.2019.00409. eCollection 2019.PMID: 31551716 
 

Alzheimer's disease-associated tau alters Drosophila circadian activity, sleep and clock neuron electrophysiology.

Buhl E, Higham JP, Hodge JJL.Neurobiol Dis. 2019 Oct;130:104507. doi: 10.1016/j.nbd.2019.104507. Epub 2019 Jun 14.PMID: 31207389 
 

Age-dependent changes in clock neuron structural plasticity and excitability are associated with a decrease in circadian output behavior and sleep.

Curran JA, Buhl E, Tsaneva-Atanasova K, Hodge JJL.
Neurobiol Aging. 2019 Feb 2;77:158-168. doi: 10.1016/j.neurobiolaging.2019.01.025.  PMID:30825692

Neuronal overexpression of Alzheimer's disease and Down's syndrome associated DYRK1A/minibrain gene alters motor decline, neurodegeneration and synaptic plasticity in Drosophila.
Lowe SA, Usowicz MM, Hodge JJL.
Neurobiol Dis. 2019 May;125:107-114. doi: 10.1016/j.nbd.2019.01.017. Epub 2019 Jan 28.
PMID:30703437

Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson's disease phenotypes.
Julienne H, Buhl E, Leslie DS, Hodge JJL.
Neurobiol Dis. 2017 Aug;104:15-23. doi: 10.1016/j.nbd.2017.04.014. Epub 2017 Apr 21.
PMID:28435104

Quasimodo mediates daily and acute light effects on Drosophila clock neuron excitability.
Buhl E, Bradlaugh A, Ogueta M, Chen KF, Stanewsky R, Hodge JJ.
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13486-13491. Epub 2016 Nov 7.
PMID:27821737

Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature.
Chen C, Buhl E, Xu M, Croset V, Rees JS, Lilley KS, Benton R, Hodge JJ, Stanewsky R.
Nature. 2015 Nov 26;527(7579):516-20. doi: 10.1038/nature16148. Epub 2015 Nov 18.
PMID:26580016

View complete publications list in the University of Bristol publications system.

Funding

2021-,"Rare inherited neurological conditions; using Drosophila models to study disease mechanisms." University of Bristol funding with Dr Anirban Majumdar, Consultant Paediatric Neurologist, £20000

2021-, “Testing the effectiveness of L-type calcium channel blockers as new repurposed Alzheimer disease drugs” Alzheimer’s Research UK small grant, £5000.

2020-, “Functional screening of novel genes associated with Alzheimer’s disease to investigate

new mechanisms, therapeutic targets and drugs” Alzheimer’s Research UK project grant, £250,000

2017-2021, “Optogenetic imaging and remote control of a fly electrical clock”, Leverhulme project grant, £210,844.

2019, “In vivo characterisation of novel risk genes for Alzheimer’s disease identified by Epigenome Wide Association Studies” Alzheimer’s Research UK small grant, £5K.

2018, “Modelling the relationship between sleep and memory Alzheimer’s disease using Drosophila” Alzheimer’s Society undergraduate grant, £2K.

2017, “Characterising a novel Alzheimer candidate gene using Drosophila” Alzheimer’s Society undergraduate grant, £2K.

2015, “Harnessing CRISPR/Cas9 technology to develop new models of Alzheimer’s” GW4 accelerator grant, £75K.

2013, “How does light control the activity and electrical properties of neurons integrating arousal behaviour, circadian rhythms, and sleep?” BBSRC research grant, £430K.

2009, “The role of PDZ scaffold dCASK and CaMKII signaling in synaptic plasticity and learning” BBSRC New investigator research grant, £542K.

2008, “Potassium channel mediated mechanisms of learning and memory in Drosophila” EU Marie-Curie International Reintegration Grant, £75K.

2008, “Using Drosophila to dissect the molecular connection between potassium channels and cancer” Royal Society Research Grant, £15K.

2006, “The role of Shaw K+ channels in Drosophila circadian rhythms” EMBO Fellowship, £7K.

Teaching

Physiology, Pharmacology and Neuroscience Postgraduate Research Director.

Pharmacology programme – 1st year, 2nd year, 3rd year and MSci lectures, practicals, tutorials and personal tutor.

Medical programme – tutorials.

Veterinary programme – lectures.

Dental programme – lectures.

MSc in Biomedical Sciences, Health Sciences and Molecular Neurosciences lectures and research projects. 

Citizenship

BBSRC panel of experts

Editor of Frontiers in Neuropharmacology and Frontiers in Physiology

School Research Committee member

Postgraduate Teaching Committee member

Organiser of South West Fly meeting, Bristol and UK clock clubs

 

http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/

https://twitter.com/doctor_fruitfly

https://twitter.com/UoBrisPPN

https://www.linkedin.com/company/university-of-bristol-school-of-physiology-pharmacology

https://www.facebook.com/uobppn

Dr James Hodge

Group

  • Dr Edgar Buhl, Postdoc, Clock neuron electrophysiology and optogenetics, circadian rhythms and sleep
  • Dr Bangfu Zhu, Postdoc, Alzheimer disease, molecular biology, imaging and behaviour
  • Hannah Clarke, PhD student with Dr Gaynor Smith (DRI, Cardiff University), Alzheimer disease, molecular biology, imaging and behaviour
  • Jessica Foley, PhD student with Dr Stephen Montgomery, "An insect model of cognitive decline and extended longevity", bioinformatics, transcriptomics, behaviour and imaging
  • Tom Parsons, MRes student, Alzheimer disease, molecular genetics, behaviour and imaging. 
  • Nicola Hill, MRes student, Parkinson disease, molecular genetics, behaviour and imaging.
  • Amy Preston, MRes student, Alzheimer disease, molecular genetics, behaviour and imaging.
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