Dr William Schafer

William Schafer

University position

Programme Leader, MRC-LMB

Dr William Schafer is pleased to consider applications from prospective PhD students.

Institutes

Medical Research Council Laboratory of Molecular Biology

Home page

http://www2.mrc-lmb.cam.ac.uk/groups/...

Research Themes

Cellular and Molecular Neuroscience

Cognitive and Behavioural Neuroscience

Interests

The fundamental nature of mental phenomena such as perception, learning and memory is one of the remaining scientific mysteries. Since the neuroanatomy of mammalian nervous systems is exceedingly complex and incompletely characterized, it is difficult to understand mechanistically how the human brain works at the level of molecules and cells. However, in simpler organisms like the nematode C. elegans, obtaining a reductionist understanding of nervous system function and behaviour is a tractable problem.

Aspects of nervous system function in which we are investigating in C. elegans include mechanosensation: how do neurons sense stimuli such as touch and pain, and how do sensory circuits integrate and process this information. We are also interested in behavioural states: how do contextual cues such as satiety and the presence of food influence behaviour through defined neural circuits, and what roles do molecules like dopamine, serotonin and neuropeptides play in these processes.

calcium transients in the C. elegans pharynx measured by the calcium-sensitive protein cameleon
Calcium transients in the C. elegans pharynx measured by the calcium-sensitive protein cameleon
Click image to view full-size

Research Focus

Keywords

C. elegans

genetics

neuroimaging

mechanosensation

behaviour

Clinical conditions

Deafness

Equipment

Behavioural analysis

Calcium imaging

Computational modelling

Microscopy

Collaborators

Cambridge

Mario de Bono

International

Monica Driscoll Web: http://lifesci.rutgers.edu/~molbio...

Sun Wook Hwang Web: http://kumcbk21.korea.ac.kr/profile...

Paul Sternberg Web: http://wormlab.caltech.edu/

Key publications

Chatzigeorgiou M, Bang S, Hwang SW, Schafer WR (2013), “tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans.” Nature Details

Chatzigeorgiou M, Schafer WR (2011), “Lateral Facilitation between Primary Mechanosensory Neurons Controls Nose Touch Perception in C. elegans.” Neuron 70(2):299-309 Details

Chatzigeorgiou M, Yoo S, Watson JD, Lee WH, Spencer WC, Kindt KS, Hwang SW, Miller DM 3rd, Treinin M, Driscoll M, Schafer WR (2010), “Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors.” Nat Neurosci 13(7):861-8 Details

Suzuki H, Thiele TR, Faumont S, Ezcurra M, Lockery SR, Schafer WR (2008), “Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis.” Nature 454(7200):114-7 Details

Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR (2007), “Caenorhabditis elegans TRPA-1 functions in mechanosensation” Nature Neurosci 10:568-577 Details

Suzuki H, Kerr R, Bianchi L, Frøkjaer-Jensen C, Slone D, Xue J, Gerstbrein B, Driscoll M, Schafer WR (2003), “In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation.” Neuron 39(6):1005-17 Details

Kerr R, Lev-Ram V, Baird G, Vincent P, Tsien RY, Schafer WR (2000), “Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans.” Neuron 26(3):583-94 Details

Waggoner LE, Zhou GT, Schafer RW, Schafer WR (1998), “Control of alternative behavioral states by serotonin in Caenorhabditis elegans.” Neuron 21(1):203-14 Details

Schafer WR, Kenyon CJ (1995), “A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans.” Nature 375(6526):73-8 Details

Publications

2014

Branicky R, Miyazaki H, Strange K, Schafer WR (2014), “The Voltage-Gated Anion Channels Encoded by clh-3 Regulate Egg Laying in C. elegans by Modulating Motor Neuron Excitability.” J Neurosci 34(3):764-75 Details

Cohen E, Chatzigeorgiou M, Husson SJ, Steuer-Costa W, Gottschalk A, Schafer WR, Treinin M (2014), “Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception.” Mol Cell Neurosci Details

Pavlovic DM, Vértes PE, Bullmore ET, Schafer WR, Nichols TE (2014), “Stochastic Blockmodeling of the Modules and Core of the Caenorhabditis elegans Connectome.” PLoS One 9(7):e97584 Details

Rabinowitch I, Chatzigeorgiou M, Zhao B, Treinin M, Schafer WR (2014), “Rewiring neural circuits by the insertion of ectopic electrical synapses in transgenic C. elegans.” Nat Commun 5:4442 Details

Schafer WR (2014), “Mechanosensory molecules and circuits in C. elegans.” Pflugers Arch Details

2013

Brown AE, Yemini EI, Grundy LJ, Jucikas T, Schafer WR (2013), “A dictionary of behavioral motifs reveals clusters of genes affecting Caenorhabditis elegans locomotion.” Proc Natl Acad Sci U S A 110(2):791-6 Details

Choi S, Chatzigeorgiou M, Taylor KP, Schafer WR, Kaplan JM (2013), “Analysis of NPR-1 Reveals a Circuit Mechanism for Behavioral Quiescence in C. elegans.” Neuron 78(5):869-80 Details

Nicosia V, Vértes PE, Schafer WR, Latora V, Bullmore ET (2013), “Phase transition in the economically modeled growth of a cellular nervous system.” Proc Natl Acad Sci U S A 110(19):7880-5 Details

Rabinowitch I, Chatzigeorgiou M, Schafer WR (2013), “A gap junction circuit enhances processing of coincident mechanosensory inputs.” Curr Biol 23(11):963-7 Details

Smith CJ, O'Brien T, Chatzigeorgiou M, Spencer WC, Feingold-Link E, Husson SJ, Hori S, Mitani S, Gottschalk A, Schafer WR, Miller DM 3rd (2013), “Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization.” Neuron 79(2):266-80 Details

Towlson EK, Vértes PE, Ahnert SE, Schafer WR, Bullmore ET (2013), “The Rich Club of the C. elegans Neuronal Connectome.” J Neurosci 33(15):6380-6387 Details

Yemini E, Jucikas T, Grundy LJ, Brown AE, Schafer WR (2013), “A database of Caenorhabditis elegans behavioral phenotypes.” Nat Methods 10(9):877-9 Details

Zhao B, Schafer WR (2013), “Neuropeptide signaling: from the gut.” Curr Biol 23(11):R481-3 Details

2012

Cohen E, Yemini E, Schafer W, Feitelson DG, Treinin M (2012), “Locomotion analysis identifies roles of mechanosensory neurons in governing locomotion dynamics of C. elegans.” J Exp Biol 215(Pt 20):3639-48 Details

Schafer WR (2012), “Tackling thermosensation with multidimensional phenotyping.” BMC Biol 10:91 Details

Wen Q, Po MD, Hulme E, Chen S, Liu X, Kwok SW, Gershow M, Leifer AM, Butler V, Fang-Yen C, Kawano T, Schafer WR, Whitesides G, Wyart M, Chklovskii DB, Zhen M, Samuel AD (2012), “Proprioceptive coupling within motor neurons drives C. elegans forward locomotion.” Neuron 76(4):750-61 Details

2011

Aoki R, Yagami T, Sasakura H, Ogura K, Kajihara Y, Ibi M, Miyamae T, Nakamura F, Asakura T, Kanai Y, Misu Y, Iino Y, Ezcurra M, Schafer WR, Mori I, Goshima Y (2011), “A seven-transmembrane receptor that mediates avoidance response to dihydrocaffeic acid, a water-soluble repellent in Caenorhabditis elegans.” J Neurosci 31(46):16603-10 Details

Brown AE, Schafer WR (2011), “Unrestrained worms bridled by the light.” Nat Methods 8(2):129-30 Details

Ezcurra M, Tanizawa Y, Swoboda P, Schafer WR (2011), “Food sensitizes C. elegans avoidance behaviours through acute dopamine signalling.” EMBO J Details

Yemini E, Kerr RA, Schafer WR (2011), “Tracking movement behavior of multiple worms on food.” Cold Spring Harb Protoc 2011(12):1483-7 Details

Yemini E, Kerr RA, Schafer WR (2011), “Illumination for worm tracking and behavioral imaging.” Cold Spring Harb Protoc 2011(12):1480-2 Details

Yemini E, Kerr RA, Schafer WR (2011), “Preparation of samples for single-worm tracking.” Cold Spring Harb Protoc 2011(12):1475-9 Details

2010

Albeg A, Smith C, Chatzigeorgiou M, Feitelson DG, Hall DH, Schafer WR, Miller DM 3rd, Treinin M (2010), “C. elegans multi-dendritic sensory neurons: Morphology and function.” Mol Cell Neurosci Details

Ben Arous J, Tanizawa Y, Rabinowitch I, Chatenay D, Schafer WR (2010), “Automated imaging of neuronal activity in freely behaving Caenorhabditis elegans.” J Neurosci Methods 187(2):229-34 Details

Chatzigeorgiou M, Grundy L, Kindt KS, Lee WH, Driscoll M, Schafer WR (2010), “Spatial asymmetry in the mechanosensory phenotypes of the C. elegans DEG/ENaC gene mec-10.” J Neurophysiol Details

Kang L, Gao J, Schafer WR, Xie Z, Xu XZ (2010), “C. elegans TRP Family Protein TRP-4 Is a Pore-Forming Subunit of a Native Mechanotransduction Channel.” Neuron 67(3):381-391 Details

Zhang M, Schafer WR, Breitling R (2010), “A circuit model of the temporal pattern generator of Caenorhabditis egg-laying behavior.” BMC Syst Biol 4:81 Details

2009

Branicky R, Schafer WR (2009), “Tyramine: a new receptor and a new role at the synapse.” Neuron 62(4):458-60 Details

Huang K-M, Cosman P, Schafer WR (2009), “Using articulated models for tracking multiple C. elegans in physical contact” J Sign Proc Syst 55: 113-126

Senti G, Ezcurra M, Löbner J, Schafer WR, Swoboda P (2009), “Worms With a Single Functional Sensory Cilium Generate Proper Neuron-specific Behavioral Output.” Genetics Details

Walker DS, Vázquez-Manrique RP, Gower NJ, Gregory E, Schafer WR, Baylis HA (2009), “Inositol 1,4,5-trisphosphate signalling regulates the avoidance response to nose touch in Caenorhabditis elegans.” PLoS Genet 5(9):e1000636 Details

2008

Branicky RS, Schafer WR (2008), “Oxygen homeostasis: how the worm adapts to variable oxygen levels.” Curr Biol 18(13):R559-60 Details

Huang KM, Cosman P, Schafer WR (2008), “Automated detection and analysis of foraging behavior in Caenorhabditis elegans.” J Neurosci Methods 171(1):153-64 Details

Partridge FA, Tearle AW, Gravato-Nobre MJ, Schafer WR, Hodgkin J (2008), “The C. elegans glycosyltransferase BUS-8 has two distinct and essential roles in epidermal morphogenesis.” Dev Biol 317(2):549-59 Details

Wang Y, Apicella A Jr, Lee SK, Ezcurra M, Slone RD, Goldmit M, Schafer WR, Shaham S, Driscoll M, Bianchi L (2008), “A glial DEG/ENaC channel functions with neuronal channel DEG-1 to mediate specific sensory functions in C. elegans.” EMBO J 27(18):2388-99 Details

Yeh E, Ng S, Zhang M, Bouhours M, Wang Y, Wang M, Hung W, Aoyagi K, Melnik-Martinez K, Li M, Liu F, Schafer WR, Zhen M (2008), “A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal activity in C. elegans.” PLoS Biol 6(3):e55 Details

Zhang M, Chung SH, Fang-Yen C, Craig C, Kerr RA, Suzuki H, Samuel AD, Mazur E, Schafer WR (2008), “A self-regulating feed-forward circuit controlling C. elegans egg-laying behavior.” Curr Biol 18(19):1445-55 Details

2007

Eimer S, Gottschalk A, Hengartner M, Horvitz HR, Richmond J, Schafer WR, Bessereau JL (2007), “Regulation of nicotinic receptor trafficking by the transmembrane Golgi protein UNC-50.” EMBO J 26(20):4313-23 Details

Ferkey DM, Hyde R, Haspel G, Dionne HM, Hess HA, Suzuki H, Schafer WR, Koelle MR, Hart AC (2007), “C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli.” Neuron 53(1):39-52 Details

Kindt KS, Quast KB, Giles AC, De S, Hendrey D, Nicastro I, Rankin CH, Schafer WR (2007), “Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans.” Neuron 55(4):662-76 Details

Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM (2007), “Guidelines on nicotine dose selection for in vivo research.” Psychopharmacology (Berl) 190(3):269-319 Details

2006

Cronin CJ, Feng Z, Schafer WR (2006), “Automated imaging of C. elegans behavior.” Methods Mol Biol 351:241-51 Details

Frøkjaer-Jensen C, Kindt KS, Kerr RA, Suzuki H, Melnik-Martinez K, Gerstbreih B, Driscol M, Schafer WR (2006), “Effects of voltage-gated calcium channel subunit genes on calcium influx in cultured C. elegans mechanosensory neurons.” J Neurobiol 66(10):1125-39 Details

Gottschalk A, Schafer WR (2006), “Visualization of integral and peripheral cell surface proteins in live Caenorhabditis elegans.” J Neurosci Methods 154(1-2):68-79 Details

Huang KM, Cosman P, Schafer WR (2006), “Machine vision based detection of omega bends and reversals in C. elegans.” J Neurosci Methods 158(2):323-36 Details

Kerr RA, Schafer WR (2006), “Intracellular Ca2+ imaging in C. elegans.” Methods Mol Biol 351:253-64 Details

Schafer WF (2006), “Genetics of egg-laying in worms.” Annu Rev Genet 40:487-509 Details

Schafer WR (2006), “Neurophysiological methods in C. elegans: an introduction.” WormBook :1-4 Details

Schafer WR (2006), “Proprioception: a channel for body sense in the worm.” Curr Biol 16(13):R509-11 Details

Tomioka M, Adachi T, Suzuki H, Kunitomo H, Schafer WR, Iino Y (2006), “The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans.” Neuron 51(5):613-25 Details

2005

Gottschalk A, Almedom RB, Schedletzky T, Anderson SD, Yates JR 3rd, Schafer WR (2005), “Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans.” EMBO J 24(14):2566-78 Details

Hilliard MA, Apicella AJ, Kerr R, Suzuki H, Bazzicalupo P, Schafer WR (2005), “In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents.” EMBO J 24(1):63-72 Details

Schafer WR (2005), “Egg-laying.” WormBook :1-7 Details

Schafer WR (2005), “Deciphering the neural and molecular mechanisms of C. elegans behavior.” Curr Biol 15(17):R723-9 Details

2004

Bianchi L, Gerstbrein B, Frøkjaer-Jensen C, Royal DC, Mukherjee G, Royal MA, Xue J, Schafer WR, Driscoll M (2004), “The neurotoxic MEC-4(d) DEG/ENaC sodium channel conducts calcium: implications for necrosis initiation.” Nat Neurosci 7(12):1337-44 Details

Feng Z, Cronin CJ, Wittig JH Jr, Sternberg PW, Schafer WR (2004), “An imaging system for standardized quantitative analysis of C. elegans behavior.” BMC Bioinformatics 5:115 Details

Fukuto HS, Ferkey DM, Apicella AJ, Lans H, Sharmeen T, Chen W, Lefkowitz RJ, Jansen G, Schafer WR, Hart AC (2004), “G protein-coupled receptor kinase function is essential for chemosensation in C. elegans.” Neuron 42(4):581-93 Details

Geng W, Cosman P, Berry CC, Feng Z, Schafer WR (2004), “Automatic tracking, feature extraction and classification of C elegans phenotypes.” IEEE Trans Biomed Eng 51(10):1811-20 Details

Kahn-Kirby AH, Dantzker JL, Apicella AJ, Schafer WR, Browse J, Bargmann CI, Watts JL (2004), “Specific polyunsaturated fatty acids drive TRPV-dependent sensory signaling in vivo.” Cell 119(6):889-900 Details

McKay JP, Raizen DM, Gottschalk A, Schafer WR, Avery L (2004), “eat-2 and eat-18 are required for nicotinic neurotransmission in the Caenorhabditis elegans pharynx.” Genetics 166(1):161-9 Details

Sanyal S, Wintle RF, Kindt KS, Nuttley WM, Arvan R, Fitzmaurice P, Bigras E, Merz DC, Hébert TE, van der Kooy D, Schafer WR, Culotti JG, Van Tol HH (2004), “Dopamine modulates the plasticity of mechanosensory responses in Caenorhabditis elegans.” EMBO J 23(2):473-82 Details

Schafer WR (2004), “Addiction research in a simple animal model: the nematode Caenorhabditis elegans.” Neuropharmacology 47 Suppl 1:123-31 Details

2003

Geng W, Cosman P, Baek JH, Berry CC, Schafer WR (2003), “Quantitative classification and natural clustering of Caenorhabditis elegans behavioral phenotypes.” Genetics 165(3):1117-26 Details

Shyn SI, Kerr R, Schafer WR (2003), “Serotonin and Go modulate functional states of neurons and muscles controlling C. elegans egg-laying behavior.” Curr Biol 13(21):1910-5 Details

2002

Baek JH, Cosman P, Feng Z, Silver J, Schafer WR (2002), “Using machine vision to analyze and classify Caenorhabditis elegans behavioral phenotypes quantitatively.” J Neurosci Methods 118(1):9-21 Details

Kindt KS, Tam T, Whiteman S, Schafer WR (2002), “Serotonin promotes G(o)-dependent neuronal migration in Caenorhabditis elegans.” Curr Biol 12(20):1738-47 Details

Schafer WR (2002), “PKG and the neural basis for behavioral phenotypes.” Neuron 36(6):991-3 Details

Schafer WR (2002), “Genetic analysis of nicotinic signaling in worms and flies.” J Neurobiol 53(4):535-41 Details

2001

Hardaker LA, Singer E, Kerr R, Zhou G, Schafer WR (2001), “Serotonin modulates locomotory behavior and coordinates egg-laying and movement in Caenorhabditis elegans.” J Neurobiol 49(4):303-13 Details

Kim J, Poole DS, Waggoner LE, Kempf A, Ramirez DS, Treschow PA, Schafer WR (2001), “Genes affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior.” Genetics 157(4):1599-610 Details

2000

Tam T, Mathews E, Snutch TP, Schafer WR (2000), “Voltage-gated calcium channels direct neuronal migration in Caenorhabditis elegans.” Dev Biol 226(1):104-17 Details

Waggoner LE, Dickinson KA, Poole DS, Tabuse Y, Miwa J, Schafer WR (2000), “Long-term nicotine adaptation in Caenorhabditis elegans involves PKC-dependent changes in nicotinic receptor abundance.” J Neurosci 20(23):8802-11 Details

Waggoner LE, Hardaker LA, Golik S, Schafer WR (2000), “Effect of a neuropeptide gene on behavioral states in Caenorhabditis elegans egg-laying.” Genetics 154(3):1181-92 Details

1999

Schafer WR (1999), “How do antidepressants work? Prospects for genetic analysis of drug mechanisms.” Cell 98(5):551-4 Details

1996

Schafer WR, Sanchez BM, Kenyon CJ (1996), “Genes affecting sensitivity to serotonin in Caenorhabditis elegans.” Genetics 143(3):1219-30 Details

1995

Dimster-Denk D, Schafer WR, Rine J (1995), “Control of RAS mRNA level by the mevalonate pathway.” Mol Biol Cell 6(1):59-70 Details

1992

Schafer WR, Rine J (1992), “Protein prenylation: genes, enzymes, targets, and functions.” Annu Rev Genet 26:209-37 Details

1990

Finegold AA, Schafer WR, Rine J, Whiteway M, Tamanoi F (1990), “Common modifications of trimeric G proteins and ras protein: involvement of polyisoprenylation.” Science 249(4965):165-9 Details

Schafer WR, Trueblood CE, Yang CC, Mayer MP, Rosenberg S, Poulter CD, Kim SH, Rine J (1990), “Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein.” Science 249(4973):1133-9 Details

1989

Schafer WR, Kim R, Sterne R, Thorner J, Kim SH, Rine J (1989), “Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans.” Science 245(4916):379-85 Details

Thorsness M, Schafer W, D'Ari L, Rine J (1989), “Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae.” Mol Cell Biol 9(12):5702-12 Details

1988

Ray C, Igo M, Shafer W, Losick R, Moran CP Jr (1988), “Suppression of ctc promoter mutations in Bacillus subtilis.” J Bacteriol 170(2):900-7 Details

1987

Igo M, Lampe M, Ray C, Schafer W, Moran CP Jr, Losick R (1987), “Genetic studies of a secondary RNA polymerase sigma factor in Bacillus subtilis.” J Bacteriol 169(8):3464-9 Details