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 whose research on the nematode worm Caenorhabditis elegans, 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">Major sperm protein</span>

Major sperm protein (MSP) is a nematode specific small protein of 126 amino acids with a molecular weight of 14 kDa. It is the key player in the motility machinery of nematodes that propels the crawling movement/motility of nematode sperm. It is the most abundant protein present in nematode sperm, comprising 15% of the total protein and more than 40% of the soluble protein. MSP is exclusively synthesized in spermatocytes of the nematodes. The MSP has two main functions in the reproduction of the helminthes: i) as cytosolic component it is responsible for the crawling movement of the mature sperm, and ii) once released, it acts as hormone on the female germ cells, where it triggers oocyte maturation and stimulates the oviduct wall to contract to bring the oocytes into position for fertilization. MSP has first been identified in Caenorhabditis elegans.

<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.

Apoptosis is the process of programmed cell death. From its early conceptual beginnings in the 1950s, it has exploded as an area of research within the life sciences community. As well as its implication in many diseases, it is an integral part of biological development.

John Graham White is an Emeritus Professor of Anatomy and Molecular Biology at the University of Wisconsin–Madison. His research interests are in the biology of the model organism Caenorhabditis elegans and laser microscopy.

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.

<span class="mw-page-title-main">SmY RNA</span>

SmY ribonucleic acids are a family of small nuclear RNAs found in some species of nematode worms. They are thought to be involved in mRNA trans-splicing.

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.

Leslie Barnett was a British biologist who worked with Francis Crick, Sydney Brenner, and Richard J. Watts-Tobin to genetically demonstrate the triplet nature of the code of protein translation through the Crick, Brenner, Barnett, Watts-Tobin et al. experiment of 1961, which discovered frameshift mutations; this insight provided early elucidation of the nature of the genetic code.

Neuroheuristics studies the dynamic relations within neuroscientific knowledge, using a transdisciplinary studies approach. It was proposed by Alessandro Villa in 2000.

<span class="mw-page-title-main">Julie Ahringer</span> American geneticist

Julie Ann Ahringer is an American/British Professor of Genetics and Genomics, Director of the Gurdon Institute and a member of the Department of Genetics at the University of Cambridge. She leads a research lab investigating the control of gene expression.

<span class="mw-page-title-main">Cell lineage</span> Developmental history of a tissue or organ

Cell lineage denotes the developmental history of a tissue or organ from the fertilized egg. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses, this starts with the originator cells and finishing with a mature cell that can no longer divide.

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

Caenorhabditis elegans- microbe interactions are defined as any interaction that encompasses the association with microbes that temporarily or permanently live in or on the nematode C. elegans. The microbes can engage in a commensal, mutualistic or pathogenic interaction with the host. These include bacterial, viral, unicellular eukaryotic, and fungal interactions. In nature C. elegans harbours a diverse set of microbes. In contrast, C. elegans strains that are cultivated in laboratories for research purposes have lost the natural associated microbial communities and are commonly maintained on a single bacterial strain, Escherichia coli OP50. However, E. coli OP50 does not allow for reverse genetic screens because RNAi libraries have only been generated in strain HT115. This limits the ability to study bacterial effects on host phenotypes. The host microbe interactions of C. elegans are closely studied because of their orthologs in humans. Therefore, the better we understand the host interactions of C. elegans the better we can understand the host interactions within the human body.

Neural circuit reconstruction is the reconstruction of the detailed circuitry of the nervous system of an animal. It is sometimes called EM reconstruction since the main method used is the electron microscope (EM). This field is a close relative of reverse engineering of human-made devices, and is part of the field of connectomics, which in turn is a sub-field of neuroanatomy.

<span class="mw-page-title-main">Warwick L. Nicholas</span> English-born Australian parasitologist

Warwick Llewellyn Nicholas (1926–2010) was an Australian zoologist known as a pioneer in the field of nematology. He was a foundational member of the Australian Society for Parasitology (ASP) and in 1964, he organised the first ASP meeting. He became President of the Society in 1978, before being an elected Fellow from 1979.

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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