Professor Roger Hardie

Roger Hardie

University position

Professor

Professor Roger Hardie is pleased to consider applications from prospective PhD students.

Departments

Department of Physiology, Development and Neuroscience

Email

rch14@cam.ac.uk

Home page

http://www.pdn.cam.ac.uk/staff/h... (personal home page)

Research Themes

Cellular and Molecular Neuroscience

Systems and Computational Neuroscience

Interests

Phototransduction, TRP channels and Calcium signalling in Drosophila

Phototransduction in the fruitfly Drosophila is an important model for G-protein coupled signalling and fascinating in its own right. We study the underlying cellular and molecular machinery using a combination of molecular genetic, physiological and computational approaches. A major interest concerns the mechanisms of activation and regulation of the light-sensitive channels. These are encoded by the trp gene, which is the defining member of the intensively studied TRP ion channel family, with ~30 mammalian isoforms widely implicated in sensory transduction and Ca2+ signalling throughout the body.

Other areas of interest include

(i) molecular mechanisms of retinal degeneration

(ii) a novel class of ligand gated chloride channel directly gated by the photoreceptor neurotransmitter histamine

(iii) voltage gated potassium channels

(iv) Sodium calcium exchange

Living, dissociated Drosophila ommatidia. The light absorbing rhabdomere has been labelled by a genetically targeted GFP-tagged ion channel protein (Kir2.1). As well as visualizing the rhabdomere, this ion channel is specifically activated by PIP2 and can be used as an electrophysiological biosensor to monitor PIP2 levels in real time in vivo
Living, dissociated Drosophila ommatidia. The light absorbing rhabdomere has been labelled by a genetically targeted GFP-tagged ion channel protein (Kir2.1). As well as visualizing the rhabdomere, this ion channel is specifically activated by PIP2 and can be used as an electrophysiological biosensor to monitor PIP2 levels in real time in vivo
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Research Focus

Keywords

phototransduction

Drosophila

TRP channels

retinal degeneration

neural circuit

Clinical conditions

Retinal degeneration

Equipment

Calcium imaging

Cell culture

Drosophila genetics

Electrophysiological recording techniques

Fluorescence microscopy

Microscopy

Whole cell patch clamp

Collaborators

Cambridge

Padinjat Raghu

United Kingdom

Mikko Juusola Web: http://www.shef.ac.uk/bms/res...

International

Craig Montell Web: http://biolchem.bs.jhmi.edu/members...

Associated News Items


    Publications

    2014

    Hardie RC (2014), “Photosensitive TRPs.” Handb Exp Pharmacol 223:795-826 Details

    2013

    Chu B, Liu CH, Sengupta S, Gupta A, Raghu P, Hardie RC (2013), “Common mechanisms regulating dark noise and quantum bump amplification in Drosophila photoreceptors.” J Neurophysiol 109(8):2044-55 Details

    Chu B, Postma M, Hardie RC (2013), “Fractional Ca(2+) currents through TRP and TRPL channels in Drosophila photoreceptors.” Biophys J 104(9):1905-16 Details

    Sengupta S, Barber TR, Xia H, Ready DF, Hardie RC (2013), “Depletion of PtdIns(4,5)P₂ underlies retinal degeneration in Drosophila trp mutants.” J Cell Sci 126(Pt 5):1247-59 Details

    2012

    Georgiev P, Toscano S, Nair A, Hardie R, Raghu P (2012), “Identification of a suppressor of retinal degeneration in Drosophila photoreceptors.” J Neurogenet 26(3-4):338-47 Details

    Hardie RC (2012), “Polarization vision: Drosophila enters the arena.” Curr Biol 22(1):R12-4 Details

    Hardie RC, Franze K (2012), “Photomechanical responses in Drosophila photoreceptors.” Science 338(6104):260-3 Details

    Hardie RC, Satoh AK, Liu CH (2012), “Regulation of arrestin translocation by Ca2+ and myosin III in Drosophila photoreceptors.” J Neurosci 32(27):9205-16 Details

    Song Z, Postma M, Billings SA, Coca D, Hardie RC, Juusola M (2012), “Stochastic, adaptive sampling of information by microvilli in fly photoreceptors.” Curr Biol 22(15):1371-80 Details

    Wardill TJ, List O, Li X, Dongre S, McCulloch M, Ting CY, O'Kane CJ, Tang S, Lee CH, Hardie RC, Juusola M (2012), “Multiple spectral inputs improve motion discrimination in the Drosophila visual system.” Science 336(6083):925-31 Details

    2011

    Abou Tayoun AN, Li X, Chu B, Hardie RC, Juusola M, Dolph PJ (2011), “The Drosophila SK channel (dSK) contributes to photoreceptor performance by mediating sensitivity control at the first visual network.” J Neurosci 31(39):13897-910 Details

    Hardie RC (2011), “A brief history of trp: commentary and personal perspective.” Pflugers Arch 461(5):493-8 Details

    Liu W, Wen W, Wei Z, Yu J, Ye F, Liu CH, Hardie RC, Zhang M (2011), “The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye.” Cell 145(7):1088-101 Details

    Rosenbaum EE, Brehm KS, Vasiljevic E, Liu CH, Hardie RC, Colley NJ (2011), “XPORT-dependent transport of TRP and rhodopsin.” Neuron 72(4):602-15 Details

    Stavenga DG, Hardie RC (2011), “Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors.” J Comp Physiol A Neuroethol Sens Neural Behav Physiol 197(3):227-41 Details

    2010

    Fain GL, Hardie R, Laughlin SB (2010), “Phototransduction and the evolution of photoreceptors.” Curr Biol 20(3):R114-24 Details

    Huang J, Liu CH, Hughes SA, Postma M, Schwiening CJ, Hardie RC (2010), “Activation of TRP channels by protons and phosphoinositide depletion in Drosophila photoreceptors.” Curr Biol 20(3):189-97 Details

    Mecklenburg KL, Takemori N, Komori N, Chu B, Hardie RC, Matsumoto H, O'Tousa JE (2010), “Retinophilin is a light-regulated phosphoprotein required to suppress photoreceptor dark noise in Drosophila.” J Neurosci 30(4):1238-49 Details

    Satoh AK, Xia H, Yan L, Liu CH, Hardie RC, Ready DF (2010), “Arrestin translocation is stoichiometric to rhodopsin isomerization and accelerated by phototransduction in Drosophila photoreceptors.” Neuron 67(6):997-1008 Details

    2009

    Hardie RC, Muallem S (2009), “Lipids in Ca2+ signalling--an introduction.” Cell Calcium 45(6):517-20 Details

    Raghu P, Hardie RC (2009), “Regulation of Drosophila TRPC channels by lipid messengers.” Cell Calcium 45(6):566-73 Details

    Yau KW, Hardie RC (2009), “Phototransduction motifs and variations.” Cell 139(2):246-64 Details

    2008

    Krause Y, Krause S, Huang J, Liu CH, Hardie RC, Weckström M (2008), “Light-dependent modulation of Shab channels via phosphoinositide depletion in Drosophila photoreceptors.” Neuron 59(4):596-607 Details

    Liu CH, Satoh AK, Postma M, Huang J, Ready DF, Hardie RC (2008), “Ca2+-dependent metarhodopsin inactivation mediated by calmodulin and NINAC myosin III.” Neuron 59(5):778-89 Details

    Pantazis A, Segaran A, Liu CH, Nikolaev A, Rister J, Thum AS, Roeder T, Semenov E, Juusola M, Hardie RC (2008), “Distinct roles for two histamine receptors (hclA and hclB) at the Drosophila photoreceptor synapse.” J Neurosci 28(29):7250-9 Details

    Yusein S, Velikova N, Kupenova P, Hardie R, Wolstenholme A, Semenov E (2008), “Altered ivermectin pharmacology and defective visual system in Drosophila mutants for histamine receptor HCLB.” Invert Neurosci 8(4):211-22 Details

    2007

    Hardie RC (2007), “Vision: dynamic platforms.” Nature 450(7166):37-9 Details

    Hardie RC (2007), “TRP channels and lipids: from Drosophila to mammalian physiology.” J Physiol 578(Pt 1):9-24 Details

    Liu CH, Wang T, Postma M, Obukhov AG, Montell C, Hardie RC (2007), “In vivo identification and manipulation of the Ca2+ selectivity filter in the Drosophila transient receptor potential channel.” J Neurosci 27(3):604-15 Details

    2006

    Rosenbaum EE, Hardie RC, Colley NJ (2006), “Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival.” Neuron 49(2):229-41 Details

    Vähäsöyrinki M, Niven JE, Hardie RC, Weckström M, Juusola M (2006), “Robustness of neural coding in Drosophila photoreceptors in the absence of slow delayed rectifier K+ channels.” J Neurosci 26(10):2652-60 Details

    Zheng L, de Polavieja GG, Wolfram V, Asyali MH, Hardie RC, Juusola M (2006), “Feedback network controls photoreceptor output at the layer of first visual synapses in Drosophila.” J Gen Physiol 127(5):495-510 Details

    2005

    Georgiev P, Garcia-Murillas I, Ulahannan D, Hardie RC, Raghu P (2005), “Functional INAD complexes are required to mediate degeneration in photoreceptors of the Drosophila rdgA mutant.” J Cell Sci 118(Pt 7):1373-84 Details

    Gu Y, Oberwinkler J, Postma M, Hardie RC (2005), “Mechanisms of light adaptation in Drosophila photoreceptors.” Curr Biol 15(13):1228-34 Details

    Hardie RC (2005), “Inhibition of phospholipase C activity in Drosophila photoreceptors by 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA) and di-bromo BAPTA.” Cell Calcium 38(6):547-56 Details

    MacPherson MR, Pollock VP, Kean L, Southall TD, Giannakou ME, Broderick KE, Dow JA, Hardie RC, Davies SA (2005), “Transient receptor potential-like channels are essential for calcium signaling and fluid transport in a Drosophila epithelium.” Genetics 169(3):1541-52 Details

    Wang T, Xu H, Oberwinkler J, Gu Y, Hardie RC, Montell C (2005), “Light activation, adaptation, and cell survival functions of the Na+/Ca2+ exchanger CalX.” Neuron 45(3):367-78 Details

    2004

    Hardie RC (2004), “Regulation of Drosophila TRP channels by lipid messengers.” Novartis Found Symp 258:160-7; discussion 167-71, 263-6 Details

    Hardie RC, Gu Y, Martin F, Sweeney ST, Raghu P (2004), “In vivo light-induced and basal phospholipase C activity in Drosophila photoreceptors measured with genetically targeted phosphatidylinositol 4,5-bisphosphate-sensitive ion channels (Kir2.1).” J Biol Chem 279(46):47773-82 Details

    2003

    Hardie RC (2003), “Phototransduction: shedding light on translocation.” Curr Biol 13(19):R775-7 Details

    Hardie RC (2003), “Regulation of TRP channels via lipid second messengers.” Annu Rev Physiol 65:735-59 Details

    Hardie RC (2003), “TRP channels in Drosophila photoreceptors: the lipid connection.” Cell Calcium 33(5-6):385-93 Details

    Hardie RC, Martin F, Chyb S, Raghu P (2003), “Rescue of light responses in the Drosophila "null" phospholipase C mutant, norpAP24, by the diacylglycerol kinase mutant, rdgA, and by metabolic inhibition.” J Biol Chem 278(21):18851-8 Details

    Niven JE, Vähäsöyrinki M, Kauranen M, Hardie RC, Juusola M, Weckström M (2003), “The contribution of Shaker K+ channels to the information capacity of Drosophila photoreceptors.” Nature 421(6923):630-4 Details

    2002

    Gengs C, Leung HT, Skingsley DR, Iovchev MI, Yin Z, Semenov EP, Burg MG, Hardie RC, Pak WL (2002), “The target of Drosophila photoreceptor synaptic transmission is a histamine-gated chloride channel encoded by ort (hclA).” J Biol Chem 277(44):42113-20 Details

    Hardie R (2002), “Adaptation through translocation.” Neuron 34(1):3-5 Details

    Hardie RC, Martin F, Cochrane GW, Juusola M, Georgiev P, Raghu P (2002), “Molecular basis of amplification in Drosophila phototransduction: roles for G protein, phospholipase C, and diacylglycerol kinase.” Neuron 36(4):689-701 Details

    2001

    Hardie RC (2001), “Phototransduction in Drosophila melanogaster.” J Exp Biol 204(Pt 20):3403-9 Details

    Hardie RC, Raghu P (2001), “Visual transduction in Drosophila.” Nature 413(6852):186-93 Details

    Hardie RC, Raghu P, Moore S, Juusola M, Baines RA, Sweeney ST (2001), “Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors.” Neuron 30(1):149-59 Details

    Juusola M, Hardie RC (2001), “Light adaptation in Drosophila photoreceptors: II. Rising temperature increases the bandwidth of reliable signaling.” J Gen Physiol 117(1):27-42 Details

    Juusola M, Hardie RC (2001), “Light adaptation in Drosophila photoreceptors: I. Response dynamics and signaling efficiency at 25 degrees C.” J Gen Physiol 117(1):3-25 Details

    2000

    Henderson SR, Reuss H, Hardie RC (2000), “Single photon responses in Drosophila photoreceptors and their regulation by Ca2+.” J Physiol 524 Pt 1:179-94 Details

    Raghu P, Colley NJ, Webel R, James T, Hasan G, Danin M, Selinger Z, Hardie RC (2000), “Normal phototransduction in Drosophila photoreceptors lacking an InsP(3) receptor gene.” Mol Cell Neurosci 15(5):429-45 Details

    Raghu P, Usher K, Jonas S, Chyb S, Polyanovsky A, Hardie RC (2000), “Constitutive activity of the light-sensitive channels TRP and TRPL in the Drosophila diacylglycerol kinase mutant, rdgA.” Neuron 26(1):169-79 Details

    1999

    Chyb S, Hevers W, Forte M, Wolfgang WJ, Selinger Z, Hardie RC (1999), “Modulation of the light response by cAMP in Drosophila photoreceptors.” J Neurosci 19(20):8799-807 Details

    Chyb S, Raghu P, Hardie RC (1999), “Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL.” Nature 397(6716):255-9 Details

    Polianovskiĭ AD, Hardie RC, Krause KH (1999), “[TRP protein in the Drosophila photoreceptors: immunolocalization of the hypothetical light-dependent calcium channel].” Zh Evol Biokhim Fiziol 35(6):506-15 Details

    1998

    Hardie RC, Raghu P (1998), “Activation of heterologously expressed Drosophila TRPL channels: Ca2+ is not required and InsP3 is not sufficient.” Cell Calcium 24(3):153-63 Details

    Yagodin S, Hardie RC, Lansdell SJ, Millar NS, Mason WT, Sattelle DB (1998), “Thapsigargin and receptor-mediated activation of Drosophila TRPL channels stably expressed in a Drosophila S2 cell line.” Cell Calcium 23(4):219-28 Details

    1997

    Hardie RC, Reuss H, Lansdell SJ, Millar NS (1997), “Functional equivalence of native light-sensitive channels in the Drosophila trp301 mutant and TRPL cation channels expressed in a stably transfected Drosophila cell line.” Cell Calcium 21(6):431-40 Details

    Reuss H, Mojet MH, Chyb S, Hardie RC (1997), “In vivo analysis of the drosophila light-sensitive channels, TRP and TRPL.” Neuron 19(6):1249-59 Details

    1996

    Hardie RC (1996), “Calcium signalling: setting store by calcium channels.” Curr Biol 6(11):1371-3 Details

    Hardie RC (1996), “Excitation of Drosophila photoreceptors by BAPTA and ionomycin: evidence for capacitative Ca2+ entry?” Cell Calcium 20(4):315-27 Details

    Hardie RC (1996), “A quantitative estimate of the maximum amount of light-induced Ca2+ release in Drosophila photoreceptors.” J Photochem Photobiol B 35(1-2):83-9 Details

    Hardie RC (1996), “INDO-1 measurements of absolute resting and light-induced Ca2+ concentration in Drosophila photoreceptors.” J Neurosci 16(9):2924-33 Details

    Hofstee CA, Henderson S, Hardie RC, Stavenga DG (1996), “Differential effects of ninaC proteins (p132 and p174) on light-activated currents and pupil mechanism in Drosophila photoreceptors.” Vis Neurosci 13(5):897-906 Details

    1995

    Hardie RC (1995), “Effects of intracellular Ca2+ chelation on the light response in Drosophila photoreceptors.” J Comp Physiol A 177(6):707-21 Details

    Hardie RC (1995), “Photolysis of caged Ca2+ facilitates and inactivates but does not directly excite light-sensitive channels in Drosophila photoreceptors.” J Neurosci 15(1 Pt 2):889-902 Details

    Hardie RC, Minke B (1995), “Phosphoinositide-mediated phototransduction in Drosophila photoreceptors: the role of Ca2+ and trp.” Cell Calcium 18(4):256-74 Details

    Hevers W, Hardie RC (1995), “Serotonin modulates the voltage dependence of delayed rectifier and Shaker potassium channels in Drosophila photoreceptors.” Neuron 14(4):845-56 Details

    Pollock JA, Assaf A, Peretz A, Nichols CD, Mojet MH, Hardie RC, Minke B (1995), “TRP, a protein essential for inositide-mediated Ca2+ influx is localized adjacent to the calcium stores in Drosophila photoreceptors.” J Neurosci 15(5 Pt 2):3747-60 Details

    1994

    Hardie RC, Minke B (1994), “Calcium-dependent inactivation of light-sensitive channels in Drosophila photoreceptors.” J Gen Physiol 103(3):409-27 Details

    Hardie RC, Minke B (1994), “Spontaneous activation of light-sensitive channels in Drosophila photoreceptors.” J Gen Physiol 103(3):389-407 Details

    Peretz A, Sandler C, Kirschfeld K, Hardie RC, Minke B (1994), “Genetic dissection of light-induced Ca2+ influx into Drosophila photoreceptors.” J Gen Physiol 104(6):1057-77 Details

    1993

    Hardie RC (1993), “Phototransduction. The invertebrate enigma.” Nature 366(6451):113-4 Details

    Hardie RC, Minke B (1993), “Novel Ca2+ channels underlying transduction in Drosophila photoreceptors: implications for phosphoinositide-mediated Ca2+ mobilization.” Trends Neurosci 16(9):371-6 Details

    Hardie RC, Peretz A, Pollock JA, Minke B (1993), “Ca2+ limits the development of the light response in Drosophila photoreceptors.” Proc Biol Sci 252(1335):223-9 Details

    Hardie RC, Peretz A, Suss-Toby E, Rom-Glas A, Bishop SA, Selinger Z, Minke B (1993), “Protein kinase C is required for light adaptation in Drosophila photoreceptors.” Nature 363(6430):634-7 Details

    1992

    Hardie RC, Minke B (1992), “The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors.” Neuron 8(4):643-51 Details

    1991

    Hardie RC (1991), “Voltage-sensitive potassium channels in Drosophila photoreceptors.” J Neurosci 11(10):3079-95 Details

    Hardie RC, Voss D, Pongs O, Laughlin SB (1991), “Novel potassium channels encoded by the Shaker locus in Drosophila photoreceptors.” Neuron 6(3):477-86 Details

    Weckström M, Hardie RC, Laughlin SB (1991), “Voltage-activated potassium channels in blowfly photoreceptors and their role in light adaptation.” J Physiol 440:635-57 Details

    1989

    Hardie RC (1989), “A histamine-activated chloride channel involved in neurotransmission at a photoreceptor synapse.” Nature 339(6227):704-6 Details

    1988

    Hardie RC (1988), “The eye of the mantid shrimp.” Nature 333(6173):499-500 Details

    Nässel DR, Holmqvist MH, Hardie RC, Håkanson R, Sundler F (1988), “Histamine-like immunoreactivity in photoreceptors of the compound eyes and ocelli of the flies Calliphora erythrocephala and Musca domestica.” Cell Tissue Res 253(3):639-46 Details

    1987

    Hardie RC (1987), “Is histamine a neurotransmitter in insect photoreceptors?” J Comp Physiol A 161(2):201-13 Details

    1983

    Hardie RC (1983), “Projection and connectivity of sex-specific photoreceptors in the compound eye of the male housefly (Musca domestica).” Cell Tissue Res 233(1):1-21 Details

    1981

    BlestAD,Hardie RC,McIntyre P,WilliamsDS (1981), “The spectral sensitivities of identified receptors and the function of retinal tiering in the principal eyes of a jumping spider” J Comp Physiol A 145,227-239

    Franceschini N, Hardie RC,Ribi W, Kirschfeld K (1981), “ Sexual dimorphism in a photoreceptor” Nature 291,241-244

    Hardie RC,Franceschini N, Ribi W,Kirschfeld K (1981), “Distribution and properties of sex-specific photoreceptors in the fly Musca domestica.” J Comp Physiol A 145,139-152

    1979

    Hardie RC (1979), “Electrophysiological analysis of the fly retina I Comparative properties of R1-6 and R7 and R8” J Comp Physiol A 129,19-33

    1978

    Laughlin SB, Hardie RC (1978), “Common strategies for light adaptation in the peripheral visual systems of fly and dragonfly” J Comp Physiol A 128,319-340