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William Schafer

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For the American politician, see William Donald Schaefer.
William Schafer
FRS
Born
William Ronald Schafer

(1964-08-29) August 29, 1964 (age 60)
Boston, Massachusetts, United States
NationalityAmerican, British
EducationLakeside High School, DeKalb County, Georgia, United States
Alma materHarvard University (AB Biology, 1986); University of California, Berkeley (PhD Biochemistry, 1991)
Scientific career
ThesisProtein prenylation in saccharomyces cervesiae (1990)
Doctoral advisorJasper Rine
Websitehttps://www2.mrc-lmb.cam.ac.uk/group-leaders/n-to-s/william-schafer/

William Ronald Schafer FRS (born August 29, 1964) 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, Fellow of the Academy of Medical Sciences, and Fellow of the Royal Society.[1]

Career

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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 prenylated, and showed that this modification is essential for membrane targeting and biological activity.[2]

As a postdoc in the lab of Cynthia Kenyon, he discovered that dopamine inhibits locomotion in C. elegans and identified the first neuronal calcium channel mutant in a screen for worms with abnormal dopamine sensitivity.[3] In 1995 he became an assistant professor at the University of California, San Diego. In 2001, he was awarded the Presidential Early Career Award for Scientists and Engineers following nomination through the National Institutes of Health.[4]

Following a sabbatical in 2004–2005, in 2006 he moved his research group to the Laboratory of Molecular Biology in Cambridge, UK. In 2020 he was elected a Fellow of the Royal Society[1]

In 2019 he was appointed full professor, part-time, in the Department of Biology at the Katholieke Universiteit Leuven.

Research

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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.[5] 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,[6][7][8] and shown that molecules such as TMCs and TRP channels play conserved sensory functions in these neurons.[9][10][11] His group has since shown that the detection of mechanical stimuli by TMC channels, which form the pore of hair cell mechanotransduction channels in humans, relies upon an intracellular ankyrin-CIB complex rather than force transmission through the cell membrane as was once thought.[12]

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.[13] More sophisticated worm trackers were later used to generate high-content phenotypic data for other behaviors such as locomotion;[14][15][16] this approach has proven very useful for precisely measuring and classifying effects of genes on the nervous system.

Connectomics and 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.[17] In 2023, his lab published the first neuropeptidergic connectome of C. elegans, which is the first extrasynaptic connectome of any organism.[18] 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[19]

References

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  1. ^ a b "William Schafer". Royal Society. Retrieved 20 September 2020.
  2. ^ Schafer WR, Kim R, Sterne R, Thorner J, Kim SH, Rine J (July 1989). "Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans". Science. 245 (4916): 379–85. Bibcode:1989Sci...245..379S. doi:10.1126/science.2569235. PMID 2569235.
  3. ^ Schafer WR, Kenyon CJ (May 1995). "A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans". Nature. 375 (6526): 73–8. Bibcode:1995Natur.375...73S. doi:10.1038/375073a0. PMID 7723846. S2CID 4327412.
  4. ^ "2001 Presidential Early Career Awards Announced". georgewbush-whitehouse.archives.gov. Retrieved 2024-12-22.
  5. ^ Kerr R, Lev-Ram V, Baird G, Vincent P, Tsien RY, Schafer WR (June 2000). "Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans". Neuron. 26 (3): 583–94. doi:10.1016/S0896-6273(00)81196-4. PMID 10896155. S2CID 311998.
  6. ^ Hilliard MA, Apicella AJ, Kerr R, Suzuki H, Bazzicalupo P, Schafer WR (January 2005). "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. PMC 544906. PMID 15577941.
  7. ^ Suzuki H, Thiele TR, Faumont S, Ezcurra M, Lockery SR, Schafer WR (July 2008). "Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis". Nature. 454 (7200): 114–7. Bibcode:2008Natur.454..114S. doi:10.1038/nature06927. PMC 2984562. PMID 18596810.
  8. ^ Suzuki H, Kerr R, Bianchi L, Frøkjaer-Jensen C, Slone D, Xue J, Gerstbrein B, Driscoll M, Schafer WR (September 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. doi:10.1016/j.neuron.2003.08.015. PMID 12971899. S2CID 11990506.
  9. ^ Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR (May 2007). "Caenorhabditis elegans TRPA-1 functions in mechanosensation". Nature Neuroscience. 10 (5): 568–77. doi:10.1038/nn1886. PMID 17450139. S2CID 13490958.
  10. ^ Chatzigeorgiou M, Yoo S, Watson JD, Lee WH, Spencer WC, Kindt KS, Hwang SW, Miller DM, Treinin M, Driscoll M, Schafer WR (July 2010). "Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors". Nature Neuroscience. 13 (7): 861–8. doi:10.1038/nn.2581. PMC 2975101. PMID 20512132.
  11. ^ Chatzigeorgiou M, Bang S, Hwang SW, Schafer WR (February 2013). "tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans". Nature. 494 (7435): 95–99. Bibcode:2013Natur.494...95C. doi:10.1038/nature11845. PMC 4021456. PMID 23364694.
  12. ^ Tang, Yi-Quan; Lee, Sol Ah; Rahman, Mizanur; Vanapalli, Siva A.; Lu, Hang; Schafer, William R. (2020-07-08). "Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels". Neuron. 107 (1): 112–125.e10. doi:10.1016/j.neuron.2020.03.026. ISSN 0896-6273. PMC 7343241. PMID 32325031.
  13. ^ Waggoner LE, Zhou GT, Schafer RW, Schafer WR (July 1998). "Control of alternative behavioral states by serotonin in Caenorhabditis elegans". Neuron. 21 (1): 203–14. doi:10.1016/S0896-6273(00)80527-9. PMID 9697864. S2CID 15043008.
  14. ^ Geng W, Cosman P, Berry CC, Feng Z, Schafer WR (October 2004). "Automatic tracking, feature extraction and classification of C elegans phenotypes". IEEE Transactions on Biomedical Engineering. 51 (10): 1811–20. CiteSeerX 10.1.1.523.8395. doi:10.1109/TBME.2004.831532. PMID 15490828. S2CID 8977741.
  15. ^ Yemini E, Jucikas T, Grundy LJ, Brown AE, Schafer WR (September 2013). "A database of Caenorhabditis elegans behavioral phenotypes". Nature Methods. 10 (9): 877–9. doi:10.1038/nmeth.2560. PMC 3962822. PMID 23852451.
  16. ^ Brown AE, Yemini EI, Grundy LJ, Jucikas T, Schafer WR (January 2013). "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): 791–6. Bibcode:2013PNAS..110..791B. doi:10.1073/pnas.1211447110. PMC 3545781. PMID 23267063.
  17. ^ Bentley B, Branicky R, Barnes CL, Chew YL, Yemini E, Bullmore ET, Vértes PE, Schafer WR (December 2016). "The Multilayer Connectome of Caenorhabditis elegans". PLOS Computational Biology. 12 (12): e1005283. arXiv:1608.08793. Bibcode:2016PLSCB..12E5283B. doi:10.1371/journal.pcbi.1005283. PMC 5215746. PMID 27984591.
  18. ^ Ripoll-Sánchez, Lidia; Watteyne, Jan; Sun, HaoSheng; Fernandez, Robert; Taylor, Seth R.; Weinreb, Alexis; Bentley, Barry L.; Hammarlund, Marc; Miller, David M.; Hobert, Oliver; Beets, Isabel; Vértes, Petra E.; Schafer, William R. (2023-11-15). "The neuropeptidergic connectome of C. elegans". Neuron. 111 (22): 3570–3589.e5. doi:10.1016/j.neuron.2023.09.043. ISSN 0896-6273. PMC 7615469. PMID 37935195.
  19. ^ Yan G, Vértes PE, Towlson EK, Chew YL, Walker DS, Schafer WR, Barabási AL (October 2017). "Network control principles predict neuron function in the Caenorhabditis elegans connectome". Nature. 550 (7677): 519–523. Bibcode:2017Natur.550..519Y. doi:10.1038/nature24056. PMC 5710776. PMID 29045391.

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