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William Schafer

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William Schafer
Born29th August 1964
Boston, USA
NationalityUSA, UK
EducationLakeside High School, DeKalb County GA, USA
Alma materHarvard University (AB Biology, 1986); University of California, Berkeley (PhD Biochemistry, 1991)
Websitehttps://www2.mrc-lmb.cam.ac.uk/group-leaders/n-to-s/william-schafer/

William Schafer is a neuroscientist and geneticist who has made important contributions to understanding the molecular and neural basis of behaviour. His work, principally in the nematode C. elegans, has used an interdisciplinary approach to investigate how small groups of neurons generate behavior, and he has pioneered methodological approaches, including optogenetic neuroimaging and automated behavioural phenotyping, that have been widely influential in the broader neuroscience field. He has made significant discoveries on the functional properties of ionotropic receptors in sensory transduction and on the roles of gap junctions and extrasynaptic modulation in neuronal microcircuits. More recently, he has applied theoretical ideas from network science and control theory to investigate the structure and function of simple neuronal connectomes, with the goal of understanding conserved computational principles in larger brains. He is an EMBO member and Welcome Investigator.

Background

Schafer trained as a geneticist and biochemist at the University of California, Berkeley, under the supervision of Jasper Rine. During his PhD research, he discovered that CAAX-box proteins in yeast, including Ras, are prenlyated, and showed that this modification is essential for membrane targeting and biological activity[1]. As a postdoc in the lab of Cynthia Kenyon, he discovered that dopamine inhibits locomotion in in C. elegans and identified the first neuronal calcium channel mutant in a screen for worms with abnormal dopamine sensitivity[2]. In 1995 he became an assistant professor at the University of California, San Diego.  Following a sabbatical in 2004-2005, in 2006 he moved his research group to the Laboratory of Molecular Biology in Cambridge.

Research

Genetically-encoded calcium indicators: The first genetically-encoded calcium indicators were developed in 1997, but they initially proved difficult to use in transgenic animals. In 2000, Schafer and his student Rex Kerr showed that the GECI yellow cameleon 2 could be used to record activity in muscles and in single neurons of transgenic worms[3]. This was the first use of an optogenetic sensor to record the dynamics of neural activity in an animal. Using this technique, Schafer and his group have characterized the properties of many identified neurons in the worm, including subtypes of mechanosensory, chemosensory and nociceptive neurons[4][5][6], and shown that molecules such as TMCs and TRP channels play conserved sensory functions in these neurons[7][8][9].

Automated phenotyping: Schafer's group also pioneered the use of automated imaging and machine vision for behavioral phenotyping. They first used an automated tracking microscope to record C. elegans behaviour over many hours and measure the timing of egg-laying; these experiments showed that worms fluctuate between behavioral states controlled by serotonin[10]. More sophisticated worm trackers were later used to generate high-content phenotypic data for other behaviors such as locomotion[11][12][13]; this approach has proven very useful for precisely measuring and classifying effects of genes on the nervous system.

Network science: Schafer has also worked with network scientists to investigate the structure of the C. elegans neural connectome. In particular, he recognised that neuromodulatory signaling, being largely extrasynaptic, forms a parallel wireless connectome whose topological features and modes of interaction with the wired connectome could be analyzed as a multiplex network[14]. Together with Laszlo Barabasi's group his group also carried out the first test of the idea that control theory can be used to predict neural function based on the topology of a complex neuronal connectome[15].

References

  1. ^ Schafer, W. R.; Kim, R.; Sterne, R.; Thorner, J.; Kim, S. H.; Rine, J. (1989-07-28). "Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans". Science (New York, N.Y.). 245 (4916): 379–385. ISSN 0036-8075. PMID 2569235.
  2. ^ Schafer, W. R.; Kenyon, C. J. (1995-05-04). "A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans". Nature. 375 (6526): 73–78. doi:10.1038/375073a0. ISSN 0028-0836. PMID 7723846.
  3. ^ Kerr, R.; Lev-Ram, V.; Baird, G.; Vincent, P.; Tsien, R. Y.; Schafer, W. R. (June 2000). "Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans". Neuron. 26 (3): 583–594. ISSN 0896-6273. PMID 10896155.
  4. ^ Hilliard, Massimo A.; Apicella, Alfonso J.; Kerr, Rex; Suzuki, Hiroshi; Bazzicalupo, Paolo; Schafer, William R. (2005-01-12). "In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents". The EMBO journal. 24 (1): 63–72. doi:10.1038/sj.emboj.7600493. ISSN 0261-4189. PMID 15577941.
  5. ^ Suzuki, Hiroshi; Thiele, Tod R.; Faumont, Serge; Ezcurra, Marina; Lockery, Shawn R.; Schafer, William R. (2008-07-03). "Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis". Nature. 454 (7200): 114–117. doi:10.1038/nature06927. ISSN 1476-4687. PMC 2984562. PMID 18596810.{{cite journal}}: CS1 maint: PMC format (link)
  6. ^ Suzuki, Hiroshi; Kerr, Rex; Bianchi, Laura; Frøkjaer-Jensen, Christian; Slone, Dan; Xue, Jian; Gerstbrein, Beate; Driscoll, Monica; Schafer, William R. (2003-09-11). "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): 1005–1017. ISSN 0896-6273. PMID 12971899.
  7. ^ Kindt, Katie S.; Viswanath, Veena; Macpherson, Lindsey; Quast, Kathleen; Hu, Hongzhen; Patapoutian, Ardem; Schafer, William R. (May 2007). "Caenorhabditis elegans TRPA-1 functions in mechanosensation". Nature Neuroscience. 10 (5): 568–577. doi:10.1038/nn1886. ISSN 1097-6256. PMID 17450139.
  8. ^ Chatzigeorgiou, Marios; Yoo, Sungjae; Watson, Joseph D.; Lee, Wei-Hsiang; Spencer, W. Clay; Kindt, Katie S.; Hwang, Sun Wook; Miller, David M.; Treinin, Millet (July 2010). "Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors". Nature Neuroscience. 13 (7): 861–868. doi:10.1038/nn.2581. ISSN 1546-1726. PMC 2975101. PMID 20512132.{{cite journal}}: CS1 maint: PMC format (link)
  9. ^ Chatzigeorgiou, Marios; Bang, Sangsu; Hwang, Sun Wook; Schafer, William R. (2013-02-07). "tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans". Nature. 494 (7435): 95–99. doi:10.1038/nature11845. ISSN 1476-4687. PMC 4021456. PMID 23364694.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ Waggoner, L. E.; Zhou, G. T.; Schafer, R. W.; Schafer, W. R. (July 1998). "Control of alternative behavioral states by serotonin in Caenorhabditis elegans". Neuron. 21 (1): 203–214. ISSN 0896-6273. PMID 9697864.
  11. ^ Geng, Wei; Cosman, Pamela; Berry, Charles C.; Feng, Zhaoyang; Schafer, William R. (October 2004). "Automatic tracking, feature extraction and classification of C elegans phenotypes". IEEE transactions on bio-medical engineering. 51 (10): 1811–1820. doi:10.1109/TBME.2004.831532. ISSN 0018-9294. PMID 15490828.
  12. ^ Yemini, Eviatar; Jucikas, Tadas; Grundy, Laura J.; Brown, André E. X.; Schafer, William R. (September 2013). "A database of Caenorhabditis elegans behavioral phenotypes". Nature Methods. 10 (9): 877–879. doi:10.1038/nmeth.2560. ISSN 1548-7105. PMC 3962822. PMID 23852451.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ Brown, André E. X.; Yemini, Eviatar I.; Grundy, Laura J.; Jucikas, Tadas; Schafer, William R. (2013-01-08). "A dictionary of behavioral motifs reveals clusters of genes affecting Caenorhabditis elegans locomotion". Proceedings of the National Academy of Sciences of the United States of America. 110 (2): 791–796. doi:10.1073/pnas.1211447110. ISSN 1091-6490. PMC 3545781. PMID 23267063.{{cite journal}}: CS1 maint: PMC format (link)
  14. ^ Bentley, Barry; Branicky, Robyn; Barnes, Christopher L.; Chew, Yee Lian; Yemini, Eviatar; Bullmore, Edward T.; Vértes, Petra E.; Schafer, William R. (December 2016). "The Multilayer Connectome of Caenorhabditis elegans". PLoS computational biology. 12 (12): e1005283. doi:10.1371/journal.pcbi.1005283. ISSN 1553-7358. PMC 5215746. PMID 27984591.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  15. ^ Yan, Gang; Vértes, Petra E.; Towlson, Emma K.; Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László (10 26, 2017). "Network control principles predict neuron function in the Caenorhabditis elegans connectome". Nature. 550 (7677): 519–523. doi:10.1038/nature24056. ISSN 1476-4687. PMC 5710776. PMID 29045391. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
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