Lab Overview

We are interested in how neural circuit activity underlies behaviour including circadian rhythms, sleep, memory and movement. We study these using Drosophila, quantitative behavioural assays, 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, epilepsy and neuropathies. We also studying the effect of neonicotinoid insecticides on fly and bee memory, 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? These are being testing in fly, mouse and computational models of clock neuron excitability.

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 mental health, ageing, drugs and diseases such as Alzheimer’s, Parkinson’s, Down’s and schizophrenia. Can novel mechanisms be identified and lead to new drugs? We test new dementia drugs in our preclinical models. Can enhanced sleep delay Alzheimer pathology and improved rhythms and sleep promote mental health.

4) The role of ion channel, tuberous sclerosis complex and novel genes in epilepsy. Developing new animal and computational models of epilepsy, identifying new mechanisms and testing new anti-epileptics in fly, in silico and human epileptic brain tissue. Matching patient genotype to best treatment, patient genotyping to develop novel treatments. Helping develop better predictors of seizures to facilitate novel anti-seizure devices. 

5) 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 fly whole brain or in vivo. Larval NMJ. Rodent SCN slice records. Organotypic cultured of human brain tissue. 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. GCaMP, chloride 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. Video tracking behaviour. Social assays. 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

Impacts include fundamental discoveries, techniques and tools developed. Discovering new mechanisms, targets and drugs for disease (which are entering international clinical trials), developing NC3Rs models and informing policy on safer pest management as well as better circadian rhythm, sleep and mental health policies and treatments. Our research is helping better diagnosis, understanding and treatments for dementia, neuropathies, epilepsy, tuber sclerosis complex and rare genetic diseases.It has provided new information, tools, techniques and targets for researchers in academia, the pharmaceutical and agrochemical industry, the healthcare sector and for public policy. Our fundamental and applied research discoveries have been featured in multiple press releases, news networks, popular science publications, blogs, social media and websites. As well as by the interdisciplinary international, industrial and clinical collaborations I have initiated and run. Likewise, the research networks I have built and maintain including SWFM, GW4-epilespy community, South-West ARUK network, Bristol and UK clock club. I am  ambassador for the Genetics Society, BBSRC committee member, PGR director, External examiner at St Andrews and University of Sheffield, Editor of Frontiers in Pharmacology and Physiology. I extend the impact of my research by extensive public engagement and teaching activities. 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

[1] El Alaoui AA, Buhl E, Galizia S, James JL Hodge, de Vivo L, Bellesi M(2022) Increased interaction between endoplasmic reticulum and mitochondria following sleep deprivation. BMS Biology

[2] Zhu BP, Parsons T, Foley C, Shaw Y, Dunckley T, Hulme C, Hodge JJL* (2022) DYRK1a antagonists rescue degeneration and behavioural deficits of in vivo models of Alzheimer’s diseases and Down’s syndrome. Scientific Reports 12:15847

[3] Sanchez Marco SB, Buhl E, Firth R, Zhu B, Gainsborough M, Beleza-Meireles A, Moore S, Caswell R, Stals K, Ellard S, Kennedy C, Hodge JJL, Majumdar A(2022) Hereditary spastic paraparesis (HSP) presenting as cerebral palsy due to ADD3 variant with mechanistic insight provided by a Drosophila g-adducin model. Clinical Genetics 102:494-502

[4] Zhu BP, Parsons T, StensenW, Svendsen JSM, FugelliA, Hodge JJL* (2022) DYRK1a inhibitor mediated rescue of Drosophila models of Alzheimer’s disease-Down Syndrome phenotypes. Frontiers in Pharmacology 12:881385

[5] Buhl E, Kim YA, Parsons T, Zhu B, Santa-Maria I, Lefort R, Hodge JJL (2022) Effects of Eph/ephrin signalling and human Alzheimer's disease-associated EphA1 on Drosophila behaviour and neurophysiology. Neurobiol Dis 170:105752

[6] Eick AK, Ogueta M, Buhl E, Hodge JJL, Stanewsky R (2022) The opposing chloride cotransporters KCC and NKCC control locomotor activity in constant light and during long days. Current Biology 32:1-19

[7] Tasman K, Rands SA, Hodge JJL* (2021) Measuring sleep, locomotor and foraging rhythmicity in the bumblebee Bombus terrestris, using Radio-Frequency Identification and Locomotor Activity Monitor setups. STAR protocols2:100598

[8] Hidalgo S, Campusano JM, Hodge JJL* (2021) The Drosophila ortholog of the schizophrenia-associated CACNA1A and CACNA1B voltage-gated calcium channels regulate memory, sleep and circadian rhythms in Drosophila. Neurobiol Dis:105394

[9] Hidalgo S, Campusano JM, Hodge JJL* (2021). Assessing olfactory, memory, social and circadian phenotypes associated with schizophrenia in a genetic model based on Rim. Translational Psychiatry 11:292

[10] Tasman K, Rands, S.A., Hodge, JJL* (2021). The power of Drosophila melanogaster for modelling insecticide effects on pollinators and identifying novel mechanisms. Frontiers in physiology12:659440

[11] Tasman K, Hidalgo S, Zhu B, Rands SA, Hodge JJL* (2021b). Neonicotinoids disrupt memory, circadian behaviour and sleep. Scientific Reports 11:2061

[12] Kratschmer P, Lowe S, Buhl E, Chen K-F, Lowe S, Kullmann DM, Hodge JJL*, Jepson JEC* (2021) Impaired pre-motor circuit activity and movement in a Drosophila model of KCNMA1-linked dyskinesia. Movement Disorders 36:1158-1169

[13] Buhl E, Kottler B, Hodge JJL, Hirth F (2021) Thermoresponsive motor behavior is mediated by ring neuron circuits in the central complex of Drosophila. Scientific Reports 11:155

[14] Tasman K, Rands SA, Hodge JJL* (2021a) The neonicotinoid insecticide imidacloprid disrupts bumblebee foraging rhythms and sleep. iScience 23:101827

[15] Hidalgo S, Castro C, Zárate RV, Valderrama BP, Hodge JJL, Campusano JM (2020) The behavioral and neurochemical characterization of a Drosophila dysbindin mutant supports the contribution of serotonin to schizophrenia negative symptoms. Neurochem Int 138:104753

[16] Smith P, Buhl E, Tsaneva-Atanasova K,Hodge JJL* (2019) Shaw and Shal voltage-gated potassium channels mediate circadian changes in Drosophila clock neuron excitability. J Physiology 597:5707-5722

[17] Higham JP, Hidalgo S, Buhl E, Hodge JJL* (2019) Restoration of olfactory memory in Drosophila overexpressing human Alzheimer’s disease associated tau by manipulation of L-type Ca²⁺ channels. Front Cell Neurosci 13:409

[18] Higham JP, Malik BR, Buhl E, Dawson JM, Ogier AS, Lunnon K, Hodge JJL* (2019). Alzheimer’s Disease Associated Genes Ankyrin and Tau Cause Shortened Lifespan and Memory Loss in Drosophila. Front Cell Neurosci13:260

[19] Buhl E, Higham JP, Hodge JJL* (2019) Alzheimer's disease-associated tau alters Drosophila circadian activity, sleep and clock neuron electrophysiology. Neurobiol Dis 130:104507

[20] Curran JA, Buhl E, Tsaneva-Atanasova K, Hodge JJL* (2019) Age-dependent changes in clock neuron structural plasticity and excitability are associated with a decrease in circadian output behavior and sleep. Neurobiol Aging 77:158-168

[21] Lowe SA, Usowicz MM, Hodge JJL* (2019) Neuronal overexpression of Alzheimer's disease and Down's syndrome associated DYRK1A/minibrain gene alters motor decline, neurodegeneration and synaptic plasticity in Drosophila. Neurobiol Dis 125:107-114

[22] Smith P, Arias R, Santa-Maria I, Sonti S, McCabe BD, Tsaneva-Atanasova K,Louis ED, Hodge JJL*, Clark LA (2018) A Drosophila Model of Essential Tremor. Scientific Reports 8:7664

[23] Shaw RE, Kottler B, Ludlow ZN, Kim D, da Silva SM, Buhl E, Hodge JJL, Hirth F, Sousa-Nunes R (2018)In vivo expansion of functionally integrated GABAergic interneurons by targeted increase in neural progenitors EMBO J 37:e98163

[24] Deakin A, Mendl M, Browne WJ, Paul ES, Hodge JJL* (2018) State-dependent judgement bias in Drosophila: evidence for evolutionarily primitive affective processes. Royal Society Biological Letters, 14:20170779

[25] Lowe SA, Hodge JJL*, Usowicz MM (2018)A third copy of the Down syndrome cell adhesion molecule (Dscam) causes synaptic and locomotor dysfunction in Drosophila. Neurobiol Dis 110:93-101

[26] Praschberger R¹/Lowe SA¹, Malintan NT, Giachello CNG, Patel N, Houlden H, Kullmann DM, Baines RA, Usowicz MM, Krishnakumar SS, Hodge JJL, Rothman JE, Jepson JEC (2017) Mutations in Membrin/GOSR2 reveal stringent secretory pathway demands of dendritic growth and synaptic integrity. Cell Reports 21:97-109

[27] Kottler B, Fiore VG, Ludlow ZN, Buhl E, Vinatier G, Faville R, Diaper DC, Stepto A, Dearlove J, Adachi Y, Brown S, Chen C, Solomon DA, White KE, Humphrey DM, Buchanan SM, Sigrist SJ, Endo K, Ito K, de Bivort B, Stanewsky R, Dolan RJ, Martin J-M, Hodge JJL, Strausfeld NJ, Hirth F (2017) A Lineage-Related Reciprocal Inhibition Circuitry for Sensory-Motor Action Selection. BioRxiv:100420

[28] Julienne H, Buhl E, Leslie DS, Hodge JJL* (2017) Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson’s disease phenotypes. Neurobiol Dis 104:15-23

[29] Zwarts L, Vulsteke V, Buhl E, Hodge JJL, Callarts P (2017) SlgA, the homologue of the human schizophrenia associated PRODH gene, acts in clock neurons to regulate Drosophila aggression. Disease models and Mechanisms 10:705-716

[30] Praschberger R¹, Lowe SA¹, Malintan NT, Giachello CNG, Patel N, Houlden H, Kullmann DM, Baines RA, Usowicz MM, Krishnakumar SS, Hodge JJL, Rothman JE, Jepson JEC (2017) Elucidating the pathophysiology of Membrin/GOSR2-mediated progressive myoclonus epilepsy from molecule to neuron. Molecular biology of the cell 28

[31] Buhl E, Bradlaugh A, Ogueta M, Chen K-F, Stanewsky R*, Hodge JJL(2016) Quasimodo mediates daily and acute light effects on Drosophila clock neuron excitability. Proceedings of the National Academy of Sciences USA 113:13486-13491

[32] Schlichting M, Menegazzi P, Lelito KR, Yao Z, Buhl E, Dalla Benetta E, Bahle A, Denike J, Hodge JJL, Helfrich-Förster C, Shafer OT (2016) A neural network underlying circadian entrainment and photoperiodic adjustment of sleep and activity. J Neuroscience 36:9084-96

[33] Deakin A, Browne WJ, Hodge JJL, Paul ES, Mendl M (2016) A Screen-Peck Task for Investigating Cognitive Bias in Laying Hens. PLoS One 11:e0158222

[34] Chen C¹/Buhl E¹, Xu M, Croset V, Rees J, Lilley KS, Benton R, Hodge JJL, Stanewsky R(2015) Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature. Nature 527:516-520

[35] Malik BR, Hodge JJL* (2014) Drosophila adult olfactory shock learning. Journal Of Visual Experimentation 90:e50107

[36] Gillespie JM, Hodge JJL* (2013) CASK regulates CaMKII autophosphorylation in control of synaptic growth and appetitive learning. Front Molecular Neuroscience 6:27

[37] Cavaliere S, Malik BR, Hodge JJL* (2013) KCNQ channels regulate age-related memory impairment. PLoS One 8:e62445

[38] Malik BR, Gillespie JM, Hodge JJL* (2013) CASK and CaMKII function in the mushroom body a’/b’ neurons during Drosophila memory formation. Front Neural Circuits 7:52

[39] Cavaliere S, Gillespie, JM, Hodge JJL* (2012) KCNQ channels show conserved ethanol block and function in ethanol behaviour. PLoS One 7:e50279

[40] Cavaliere S, Gillespie JM, Malik, BR, Hodge JJL* (2012) Drosophila KCNQ channel show conserved ethanol block and function in ethanol behavior and age-dependent memory decline. J Neurogenetics 26:11-12

[41] Gillespie JM, Hodge JJL* (2012) CASK and CaMKII: molecular mechanisms of learning and memory. J Neurogenetics 26:72

[42] Cavaliere S, Hodge JJL* (2011) Drosophila KCNQ channel displays evolutionarily conserved electrophysiology and pharmacology with mammalian KCNQ channels. PLoS One 6:e23898

[43] Malik BR, Gillespie JM, Hodge JJL* (2010) The role of CASK and CaMKII in synaptic plasticity and learning. J Neurogenetics 24:27-28

[44] Cavaliere S, Hodge JJL* (2010) Evolutionarily conserved KCNQ channel function. Journal of Neurogenetics:10

[45] Malik BR, Gillespie JM, Hodge JJL* (2010) The role of CASK and CaMKII in synaptic plasticity and learning. J Neurogenetics 24: 27-28

[46] Hodge JJL*, Stanewsky, R (2009) Function of the Shaw potassium channel within the Drosophila clock. Comp Biochem Physiol A 2 153: 156

[47] Parisky KM, Agosto J, Pulver S, Shang Y, Kuklin E, Hodge JJL, Kang K, Liu X, Garrity P, Rosbash M, Griffith LC (2008) The PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit.Neuron 60:672-82

[48] Hodge JJL*, Stanewsky R (2008) Function of the Shaw potassium channel within the Drosophila circadian clock. PLoS One 3:e2274

[49] Hodge JJL, Mullasseril P, Griffith LC (2006) Activity-dependent gating of CaMKII autonomous activity by Drosophila CASK. Neuron 51:327-337

[50] Hodge JJL, Mullasseril P, Griffith LC (2006) Activity-dependent gating of CaMKII autonomous activity by Drosophila Camguk. J Neurogenetics:121-122

[51] Hodge JJL, Choi JC, Griffith LC (2006) Shaw potassium channel in Drosophila. J Neurogenetics:129-130

[52] Hodge JJL, Choi JC, O’Kane CJ, Griffith LC (2005) Shaw potassium channel genes in Drosophila. J Neurobiology 63:235-254

[53] Sun XX, Hodge JJL, Zhou Y, Nguyen M, Griffith LC (2004) The eag potassium channel binds and locally activates calcium/calmodulin-dependent protein kinase II. J Biol Chem 279:10206-10214

[54] Lu CS¹/Hodge JJL¹, Mehren J, Sun XX, Griffith LC (2003) Regulation of the Ca²⁺/CaM-responsive pool of CaMKII by scaffold-dependent autophosphorylation. Neuron 40:1185-97

[55] Park D, Coleman MJ, Hodge JJL, Budnik V, Griffith LC (2002) Regulation of neuronal excitability in Drosophila by constitutively active CaMKII. J Neurobiology 52:24-42

 

Review articles (Refereed):

[56] Malik BR, Hodge JJL* (2014) CASK and CaMKII function in memory. Front Neurosci 8:178

[57] Hodge JJL* (2009) Ion channels to inactivate neurons in Drosophila. Frontiers in Molecular Neuroscience 2:13

[58] Hodge JJL* (2009) The role of PDZ scaffold CASK and CaMKII signaling in synaptic plasticity and learning in Drosophila. Comp. Biochem. Physiol. A 153:2

[59] Hodge JJL* (2013) Scientists identify “memory switch” trigger. BBSRC business article.

 

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

Funding

2023-(28), Jazz Pharmaceuticals / GW Pharma Industrial Funding, “The UK Natural history of epilepsy and standards of care in Tuberous Sclerosis Complex”, £304,751, Principle Investigator (PI), Full Time Equivalent (FTE) = 10.7%.   

2023-(26), MRC, “Mental Health and Circadian Science Network”, £780,757, co-PI, 0.72%.

2021-(25), BBSRC, “Building a membrane circadian clock across evolution”, £580,656, PI, 10%.  

2020-(24), WT, “Investigating Alzheimer’s Disease risk genes in Drosophila melanogaster”, £105,286, co-PI, 1%.  

2020-(23), ARUK, “Functional screening of novel genes associated with Alzheimer’s disease to investigate new mechanisms, therapeutic targets and drugs”, £250,000, PI, 10%.

2022-(23), ARUK, “Enhancing sleep to delay the progression of tauopathy”, £49,995, co-PI, 1%.

2022-(23) GW4 “Epilepsy community for parallel human and fly genetics, electrophysiology, modelling and drug screens” £20,000, PI, 5%.

2017-(23), Industry, Genetics and Biochemistry Society “UK and Bristol Clock Club”, £7000, PI, 1%.

2016-(23), Genetics Society, “South West Fly Meeting”, £7000, PI, 1%.

2021-(22), Alicia Koplowitz Foundation Fellowship (AKFF), “Rare inherited neurological conditions; pilot project looking at feasibility of using animal models to study disease mechanisms”, £20,000, PI, 1%.   

2021, ARUK, “Testing the effectiveness of L-type calcium channel blockers as new repurposed Alzheimer disease drugs”, £5,000, PI, 1%.

2019-20, ARUK, “In vivo characterisation of novel risk genes for Alzheimer’s disease identified by Epigenome Wide Association Studies” £5000, PI, 1%.

2018-19, AS, “Modelling the relationship between sleep and memory Alzheimer’s disease using Drosophila”, £1900, PI, 1%.

2017-21, Leverhulme Trust (LT), “Optogenetic imaging and remote control of a fly electrical clock”, £210,844, PI, 10.

2017-18, AS, “Characterising a novel Alzheimer candidate gene using Drosophila” £1900, PI, 1%.

2015-16, GW4, “Harnessing CRISPR/Cas9 technology to develop new models of Alzheimer’s” £75,000, Co-PI, 5%.

2013-17, BBSRC, “How does light control the activity and electrical properties of neurons integrating arousal behaviour, circadian rhythms, and sleep?”, £430,069, PI, 10%.

2013-17, WT, “Using Drosophila to model non-motor symptoms of Parkinson’s disease”, £125,000, PI, 5%.

2009-12, BBSRC“The role of PDZ scaffold dCASK and CaMKII signaling in synaptic plasticity and learning” £541,810, PI, 30%.

2009-13, WT, “The role of PDZ scaffolding protein CASK and CaMKII in synaptic plasticity and learning of Drosophila larvae” £125,000, PI, 2009-2013, 5%.

2008-12, EU Marie-Curie Grant, “Potassium channel mediated mechanisms of learning and memory in Drosophila” £75,000, PI, 5%.

2008-09, Royal Society (RS), “Using Drosophila to dissect the molecular connection between potassium channels and cancer”, £15,000, PI, 5%.

2006-07, EMBO Fellowship, “The role of Shaw K⁺ channels in Drosophila circadian rhythms” £7,000, PI, 100%.

Teaching

Physiology, Pharmacology and Neuroscience Postgraduate Research Director.

Pharmacology programme – 1^st year, 2^nd year, 3^rd 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

Genetics Society Ambassador and Special Interest Group leader

Editor of Frontiers in Neuropharmacology and Frontiers in Physiology

School Research Committee member

Postgraduate Teaching Committee member

Organiser of South West Fly meeting, GW4-South West Epilepsy community, Bristol and UK clock clubs

My research:

https://www.linkedin.com/in/james-hodge-7b569830/,

https://www.youtube.com/watch?v=MoS-9HgzCro, 

LIFE WITH CASK (youtube.com)

https://twitter.com/doctor_fruitfly.

Research networks and social media I have set up and run:

South West Fly meetings (SWFM): https://genetics.org.uk/events/fly-south-west/  http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/

GW4 Southwest Epilepsy Community: http://www.bristol.ac.uk/phys-pharm-neuro/events/gw4ec/ 

Bristol Clock Club: http://www.bristol.ac.uk/phys-pharm-neuro/events/uk-clock-club/ 

UK Clock Club: https://www.bioclocks.uk/

PPN social media sites: https://twitter.com/UoBrisPPN  

https://www.facebook.com/uobppn

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