Eileen Southgate

Last updated
Eileen Southgate
NationalityBritish
Known formapping C. elegans nervous system
Scientific career
Fields Biology, Biochemistry
Institutions Medical Research Council Laboratory of Molecular Biology
Academic advisors Max Perutz, Sydney Brenner, Vernon Ingram

Eileen Southgate is a British biologist who mapped the complete nervous system of the roundworm Caenorhabditis elegans (C. elegans), together with John White, Nichol Thomson, and Sydney Brenner. The work, done largely by hand-tracing thousands of serial section electron micrographs, was the first complete nervous system map of any animal [1] and it helped establish C. elegans as a model organism. [2] Among other projects carried out as a laboratory assistant at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB), Southgate contributed to work on solving the structure of hemoglobin with Max Perutz and John Kendrew, [3] and investigating the causes of sickle cell disease with Vernon Ingram. [4]

Contents

Career

Southgate spent her entire career as a laboratory technician at the Medical Research Council Laboratory of Molecular Biology (MRC LMB). [3] She began working there in 1956, at the age of 16, after being given the option by a career officer who came to her school. [3]

Southgate initially worked for Max Perutz and John Kendrew studying hemoglobin, the protein responsible for carrying oxygen throughout the bloodstream, and the related protein myoglobin. Among other jobs, she was tasked with helping prepare hemoglobin and myoglobin for x-ray crystallography, a technique used to determine the structures of crystallized molecules such as proteins, based on how they interact with x-ray beams to produce a diffraction pattern. [4] Thanks in part to Southgate's assistance, Perutz and Kendrew solved crystal structures of hemoglobin and myoglobin, winning them the 1962 Nobel Prize in chemistry for “for being the first to successfully identify the structures of complex proteins.” [5] Southgate carried out additional research on hemoglobin with Vernon Ingram, assisting with his research on sickle cell disease, a genetic disease in which a mutation in hemoglobin causes it to form chains (polymerize) and block blood vessels. [4]

In 1962, Southgate briefly worked with Reuben Lebermen on his studies of plant viruses; she grew the plants, which were then infected by viruses he wanted to study, then she harvested them and purified out the viral particles. [4] She then went to work for Tony Stretton, where after initial work involved helping him investigate β-galactosidase, [4] she aided in his exploration of the nervous system of the parasitic nematode Ascaris lumbricoides using light microscopy. [6] When Stretton left for the University of Wisconsin in 1971, Southgate went to work with John White, who was then a PhD student under Sydney Brenner. [6]

Brenner was interested in establishing C. elegans as a model organism at MRC LMB, and using it to study the nervous system and its connection to genetics. [2] In pursuit of this goal, he wanted to obtain a complete map of the C. elegans nervous system, and Southgate was tasked with helping John White and electron microscopist Nichol Thomas achieve this. C. elegans is around 100 times smaller than Ascaris (~1mm compared to ~10 cm), so they had to use a higher-resolution imaging technique, electron microscopy. [2] Nichol Thomson helped prepare thousands of serial transverse sections of C. elegans worms, which Southgate imaged, printed out, and traced. She labeled the cell bodies, processes, and connections in each image and worked with John White to trace each neuron's journey through the worm. [6] The process took close to 15 years and culminated in a 340-page-long paper published in 1986 in the Philosophical Transactions of the Royal Society B . Officially titled “The structure of the nervous system of the nematode Caenorhabditis elegans,” [7] it is commonly referred to by its running title, “The Mind of a Worm.” [2] They identified 302 neurons in the hermaphrodite C. elegans worm, which they grouped into 118 classes, and they discovered that the layout and connections were virtually the same in genetically-identical worms. [2] They found close to 8,000 total synapses (cell to cell connections) which included around 2000 neuromuscular junctions, 5000 chemical synapses & 600 gap junctions (where communication is through electrical signals). [1] Having the map helped establish C. elegans as a model organism and allowed for further research into neural circuitry and the genes involved in establishing C. elegans' neural layout. [2] Additionally, it aided researchers in studying analogous nerves other nematodes, including Ascaris, which, due to its larger size, is more amenable to electrophysiological investigation. [8] Southgate retired in 1993. [4]

Bibliography

Related Research Articles

<i>Caenorhabditis elegans</i> Free-living species of nematode

Caenorhabditis elegans is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek caeno- (recent), rhabditis (rod-like) and Latin elegans (elegant). In 1900, Maupas initially named it Rhabditides elegans. Osche placed it in the subgenus Caenorhabditis in 1952, and in 1955, Dougherty raised Caenorhabditis to the status of genus.

<span class="mw-page-title-main">Neuroanatomy</span> Branch of neuroscience

Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems. Their neuroanatomy is therefore better understood. In vertebrates, the nervous system is segregated into the internal structure of the brain and spinal cord and the series of nerves that connect the CNS to the rest of the body. Breaking down and identifying specific parts of the nervous system has been crucial for figuring out how it operates. For example, much of what neuroscientists have learned comes from observing how damage or "lesions" to specific brain areas affects behavior or other neural functions.

<span class="mw-page-title-main">Sydney Brenner</span> South African biologist and Nobel prize winner

Sydney Brenner was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to work on the genetic code, and other areas of molecular biology while working in the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England. He established the roundworm Caenorhabditis elegans as a model organism for the investigation of developmental biology, and founded the Molecular Sciences Institute in Berkeley, California, United States.

<span class="mw-page-title-main">John Kendrew</span> English biochemist and crystallographer

Sir John Cowdery Kendrew, was an English biochemist, crystallographer, and science administrator. Kendrew shared the 1962 Nobel Prize in Chemistry with Max Perutz, for their work at the Cavendish Laboratory to investigate the structure of haem-containing proteins.

<span class="mw-page-title-main">H. Robert Horvitz</span> American biologist

Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM is an American biologist best known for his research on the nematode worm Caenorhabditis elegans, for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston, whose "seminal discoveries concerning the genetic regulation of organ development and programmed cell death" were "important for medical research and have shed new light on the pathogenesis of many diseases".

<span class="mw-page-title-main">John Sulston</span> British biologist and academic (1942–2018)

Sir John Edward Sulston was a British biologist and academic who won the Nobel Prize in Physiology or Medicine for his work on the cell lineage and genome of the worm Caenorhabditis elegans in 2002 with his colleagues Sydney Brenner and Robert Horvitz at the MRC Laboratory of Molecular Biology. He was a leader in human genome research and Chair of the Institute for Science, Ethics and Innovation at the University of Manchester. Sulston was in favour of science in the public interest, such as free public access of scientific information and against the patenting of genes and the privatisation of genetic technologies.

<span class="mw-page-title-main">MRC Laboratory of Molecular Biology</span> Research institute in Cambridge, England

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory at the forefront of scientific discovery, dedicated to improving the understanding of key biological processes at atomic, molecular and cellular levels using multidisciplinary methods, with a focus on using this knowledge to address key issues in human health.

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<span class="mw-page-title-main">Animal testing on invertebrates</span> Overview article

Most animal testing involves invertebrates, especially Drosophila melanogaster, a fruit fly, and Caenorhabditis elegans, a nematode. These animals offer scientists many advantages over vertebrates, including their short life cycle, simple anatomy and the ease with which large numbers of individuals may be studied. Invertebrates are often cost-effective, as thousands of flies or nematodes can be housed in a single room.

Barbara J. Meyer is a biologist and genetist, noted for her pioneering research on lambda phage, a virus that infects bacteria; discovery of the master control gene involved in sex determination; and studies of gene regulation, particularly dosage compensation. Meyer's work has revealed mechanisms of sex determination and dosage compensation—that balance X-chromosome gene expression between the sexes in Caenorhabditis elegans that continue to serve as the foundation of diverse areas of study on chromosome structure and function today.

The nematode worm Caenorhabditis elegans was first studied in the laboratory by Victor Nigon and Ellsworth Dougherty in the 1940s, but came to prominence after being adopted by Sydney Brenner in 1963 as a model organism for the study of developmental biology using genetics. In 1974, Brenner published the results of his first genetic screen, which isolated hundreds of mutants with morphological and functional phenotypes, such as being uncoordinated. In the 1980s, John Sulston and co-workers identified the lineage of all 959 cells in the adult hermaphrodite, the first genes were cloned, and the physical map began to be constructed. In 1998, the worm became the first multi-cellular organism to have its genome sequenced. Notable research using C. elegans includes the discoveries of caspases, RNA interference, and microRNAs. Six scientists have won the Nobel prize for their work on C. elegans.

<span class="mw-page-title-main">Bob Waterston</span>

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Host microbe interactions in <i>Caenorhabditis elegans</i>

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References

  1. 1 2 Emmons, Scott W. (2015-04-19). "The beginning of connectomics: a commentary on White et al. (1986) 'The structure of the nervous system of the nematode Caenorhabditis elegans'". Philosophical Transactions of the Royal Society B: Biological Sciences. 370 (1666): 20140309. doi:10.1098/rstb.2014.0309. ISSN   0962-8436. PMC   4360118 . PMID   25750233.
  2. 1 2 3 4 5 6 Ankeny, Rachel A. (June 2001). "The natural history of Caenorhabditis elegans research". Nature Reviews Genetics. 2 (6): 474–479. doi:10.1038/35076538. ISSN   1471-0064. PMID   11389464. S2CID   10015950.
  3. 1 2 3 Brown, Andrew, 1955- (2004). In the beginning was the worm : finding the secrets of life in a tiny hermaphrodite. Pocket. ISBN   0-7434-1598-1. OCLC   53388833.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  4. 1 2 3 4 5 6 Finch, John (2013-11-11). A Nobel Fellow on Every Floor: A History of the Medical Research Council Laboratory of Molecular Biology. Icon Books. ISBN   978-1-84831-670-6.
  5. ↑ Kirk, Rebecca (August 2014). "The first of its kind". Nature. 511 (7509): 13. doi: 10.1038/nature13360 . ISSN   1476-4687.
  6. 1 2 3 "Getting into the mind of a worm—a personal view". www.wormbook.org. Retrieved 2020-02-14.
  7. ↑ White, John Graham; Southgate, Eileen; Thomson, J. N.; Brenner, Sydney (1986-11-12). "The structure of the nervous system of the nematode Caenorhabditis elegans". Philosophical Transactions of the Royal Society of London. B, Biological Sciences. 314 (1165): 1–340. doi:10.1098/rstb.1986.0056. PMID   22462104.
  8. ↑ Lewin, R. (1984-07-13). "The continuing tale of a small worm". Science. 225 (4658): 153–156. doi:10.1126/science.6729473. ISSN   0036-8075. PMID   6729473.


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