Elizabeth Fisher (neuroscientist)

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Elizabeth Fisher
FMedSci FRSB
Born
Elizabeth Mary Claire Fisher
Alma mater University of Oxford (BSc)
Imperial College London (PhD)
Scientific career
Institutions Massachusetts Institute of Technology
Imperial College London
University College London
Thesis Microcloning and molecular mapping of the mouse X chromosome  (1987)
Doctoral advisors Mary F. Lyon
Stephen Brown
Website iris.ucl.ac.uk/iris/browse/profile?upi=EMCFI97

Elizabeth Mary Claire Fisher FMedSci FRSB [1] is a British geneticist and Professor at University College London. Her research investigates the degeneration of motor neurons during amyotrophic lateral sclerosis and Alzheimer's disease triggered by Down syndrome. [2]

Contents

Education

Fisher studied physiological sciences at the University of Oxford [3] where she was an undergraduate student at St Anne's College, Oxford in 1981. [3] After completing her undergraduate studies Fisher left science and trained as a typist and worked in several different jobs in UK and Australia [4] and in 1983 moved to Imperial College London, where she worked on mouse molecular genetics. At St Mary's Hospital, London Fisher completed microdissection on the mouse X chromosome. [3] During her doctoral research she worked alongside Mary F. Lyon and Stephen Brown at the Medical Research Council in Harwell. [5] [6] She dissected individual chromosomes and cloned DNA fragments into plasmids.

Career and research

After graduating from Imperial College London in 1986, Fisher moved to the United States, where she was appointed a postdoctoral fellow at Massachusetts Institute of Technology (MIT). At MIT, Fisher worked as a postdoc in the lab of David C. Page on Turner syndrome. Her early work looked at the male sex determining factor and then considered the genes responsible for Turner syndrome. [3] Fisher returned to Imperial College London in 1990, when she was awarded a Royal Society University Research Fellowship to start an independent research group looking at aneuploidy. [3] [6] In collaboration with Victor Tybulewicz of the MRC, she was awarded Wellcome Trust research funding in 1991, which allowed her to expand her research into a new model of Down syndrome. [7] In 2001 Fisher was appointed Professor at University College London and in 2017 she also set up a lab at the Medical Research Council Mouse Genetics Unit in Harwell. [3] Her research considers motor neuron degeneration, genome editing and the development of mouse models to understand neurological disorders. [8]

Fisher received the 2011 Faculty Member of the Year Award for Neurological Disorders on Faculty of 1000 (F1000) and an Addgene Blue Flame Award in 2017 for depositing a plasmid that has been shared more than 100 times. Fisher serves as an academic editor on the journal PLoS Genetics and on the boards for the journals Disease Models and Mechanism, Mammalian Genome. [9]

In 2003, work from Fisher's lab provided one of the first demonstrations in a mammalian model of the link between defects in retrograde transport and neurodegeneration. In a paper published in Science, Fisher found that two spontaneous mouse mutants generated from an ENU (N-ethyl-N-nitrosourea) screen harbored missense point mutations in the cytoplasmic dynein heavy chain gene. In cells, dynein is the motor protein that moves cargos toward the minus end of microtubules. These mutants were named Loa (Legs at odd angles) and Cra1 (Cramping 1) due to the phenotypes of body twisting and hindlimb clenching when suspended by the tail. Heterozygotes show locomotion defects with neuronal loss. Homozygotes are unable to feed and move and die within 24 hours of birth, but embryonic neurons have intracellular inclusions that are positive for ubiquitin, SOD, CDK5, and neurofilament. [10]

Fisher and Tybulewicz have demonstrated that mouse models can be used to understand the genes that give rise to certain aspects of Down syndrome. [11] Fisher and Tybulewicz were the first to successfully introduce an almost full-length human chromosome into mice – a significant technical achievement, as it had previously only been possible to introduce small fragments of chromosomes. [12] People with Down syndrome, a condition which occurs due to trisomy on Chromosome 21, are particularly susceptible to Alzheimer's disease. The mouse models that Fisher and Tybulewicz created have allowed scientists to study the genes responsible for complex conditions, which allows her to design synthetic chromosomes for gene therapy. [12] [13] Fisher has investigated a series of proteins that are modified by Alzheimer's disease and impacted by trisomy. [3]

Fisher develops new models for Amyotrophic lateral sclerosis (ALS) that occurs due to mutations in the gene FUS. [3] ALS is a form of motor neuron disease that occurs during middle age, whereas spinal muscular atrophy is the most common genetic killer of children. [3] Whilst it is well known that certain genes cause motor neuron disease, it is not clear how mutations impact the disease progression. Working with Medical Research Council Harwell; Fisher has looked at the molecular changes that occur during ALS. She has investigated how the RNA-binding protein mutant FUS behaves in mouse models. [14] Fisher serves as a Council Member at the Academy of Medical Sciences. [15]

Selected publications

Awards and honours

She was elected a Fellow of the Academy of Medical Sciences (FMedSci) in 2007 [1] and a Fellow of the Royal Society of Biology (FRSB) in 2010.[ citation needed ] She was made a Faculty of 1000 member in 2010. [19] In 2013 she was elected to Academia Net. [20] In 2019 Fisher appeared on The Life Scientific . [4]

Related Research Articles

<span class="mw-page-title-main">Rett syndrome</span> Genetic brain disorder

Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often have slower growth, difficulty walking, and a smaller head size. Complications of Rett syndrome can include seizures, scoliosis, and sleeping problems. The severity of the condition is variable.

<span class="mw-page-title-main">FOXP2</span> Transcription factor gene of the forkhead box family

Forkhead box protein P2 (FOXP2) is a protein that, in humans, is encoded by the FOXP2 gene. FOXP2 is a member of the forkhead box family of transcription factors, proteins that regulate gene expression by binding to DNA. It is expressed in the brain, heart, lungs and digestive system.

<span class="mw-page-title-main">Lissencephaly</span> Medical condition

Lissencephaly is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in a lack of development of brain folds (gyri) and grooves (sulci). It is a form of cephalic disorder. Terms such as agyria and pachygyria are used to describe the appearance of the surface of the brain.

<span class="mw-page-title-main">Peripherin</span> Protein-coding gene in the species Homo sapiens

Peripherin is a type III intermediate filament protein expressed mainly in neurons of the peripheral nervous system. It is also found in neurons of the central nervous system that have projections toward peripheral structures, such as spinal motor neurons. Its size, structure, and sequence/location of protein motifs is similar to other type III intermediate filament proteins such as desmin, vimentin and glial fibrillary acidic protein. Like these proteins, peripherin can self-assemble to form homopolymeric filamentous networks, but it can also heteropolymerize with neurofilaments in several neuronal types. This protein in humans is encoded by the PRPH gene. Peripherin is thought to play a role in neurite elongation during development and axonal regeneration after injury, but its exact function is unknown. It is also associated with some of the major neuropathologies that characterize amyotropic lateral sclerosis (ALS), but despite extensive research into how neurofilaments and peripherin contribute to ALS, their role in this disease is still unidentified.

<span class="mw-page-title-main">Sex-determining region Y protein</span> Protein that initiates male sex determination in therian mammals

Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.

<span class="mw-page-title-main">Rubinstein–Taybi syndrome</span> Rare genetic condition

Rubinstein–Taybi syndrome (RTS) is a rare genetic condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary among affected individuals. These characteristics are caused by a mutation or deletion in the CREBBP gene, located on chromosome 16, and/or the EP300 gene, located on chromosome 22.

<span class="mw-page-title-main">Mary F. Lyon</span> English geneticist (1925–2014)

Mary Frances Lyon was an English geneticist best known for her discovery of X-chromosome inactivation, an important biological phenomenon.

Neurturin (NRTN) is a protein that is encoded in humans by the NRTN gene. Neurturin belongs to the glial cell line-derived neurotrophic factor (GDNF) family of neurotrophic factors, which regulate the survival and function of neurons. Neurturin’s role as a growth factor places it in the transforming growth factor beta (TGF-beta) subfamily along with its homologs persephin, artemin, and GDNF. It shares a 42% similarity in amino acid sequence with mature GDNF. It is also considered a trophic factor and critical in the development and growth of neurons in the brain. Neurotrophic factors like neurturin have been tested in several clinical trial settings for the potential treatment of neurodegenerative diseases, specifically Parkinson's disease.

<span class="mw-page-title-main">Unconventional myosin-Va</span> Protein-coding gene in the species Homo sapiens

Unconventional myosin-Va is a motor protein in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments. In humans it is coded for by the MYO5A gene.

<span class="mw-page-title-main">SOD1</span> Protein-coding gene in the species Homo sapiens

Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, familial amyotrophic lateral sclerosis and Parkinson's disease.

<span class="mw-page-title-main">SOX9</span> Transcription factor gene of the SOX family

Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.

<span class="mw-page-title-main">SHANK3</span> Protein-coding gene in humans

SH3 and multiple ankyrin repeat domains 3 (Shank3), also known as proline-rich synapse-associated protein 2 (ProSAP2), is a protein that in humans is encoded by the SHANK3 gene on chromosome 22. Additional isoforms have been described for this gene but they have not yet been experimentally verified.

<span class="mw-page-title-main">Huda Zoghbi</span> Lebanese scientist

Huda Yahya Zoghbi, born Huda El-Hibri, is a Lebanese-born American geneticist, and a professor at the Departments of Molecular and Human Genetics, Neuroscience and Neurology at the Baylor College of Medicine. She is the director of the Jan and Dan Duncan Neurological Research Institute. She became the editor of the Annual Review of Neuroscience as of 2018.

<span class="mw-page-title-main">UCL Queen Square Institute of Neurology</span> Academic institution in United Kingdom

The UCL Queen Square Institute of Neurology is an institute within the Faculty of Brain Sciences of University College London (UCL) and is located in London, United Kingdom. Together with the National Hospital for Neurology and Neurosurgery, an adjacent facility with which it cooperates closely, the institute forms a major centre for teaching, training and research in neurology and allied clinical and basic neurosciences.

<span class="mw-page-title-main">SATB2</span> Protein-coding gene in the species Homo sapiens

Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene. SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling. SATB2 shows a restricted mode of expression and is expressed in certain cell nuclei. The SATB2 protein is mainly expressed in the epithelial cells of the colon and rectum, followed by the nuclei of neurons in the brain.

<span class="mw-page-title-main">Congenital mirror movement disorder</span> Medical condition

Congenital mirror movement disorder(CMM disorder) is a rare genetic neurological disorder which is characterized by mirrored movement, sometimes referred to as associated or synkinetic movement, most often in the upper extremity of the body. These movements are voluntary intentional movements on one, ipsilateral, side of the body that are mirrored simultaneously by involuntary movements on the contralateral side.

<span class="mw-page-title-main">Stephen D. M. Brown</span>

Steve David Macleod Brown is director of the Medical Research Council (MRC) Mammalian Genetics Unit, MRC Harwell at Harwell Science and Innovation Campus, Oxfordshire, a research centre on mouse genetics. In addition, he leads the Genetics and Pathobiology of Deafness research group.

Catherine Abbott, Lady Bird is a professor of molecular genetics at the University of Edinburgh.

David L. Nelson is an American human geneticist, currently an associate director at the Intellectual and Developmental Disabilities Research Center (1995), and professor at the Department of Molecular and Human Genetics at Baylor College of Medicine BCM since 1999. Since 2018, he is the director at the Cancer and Cell Biology Ph.D program, and the director of Integrative Molecular and Biomedical Sciences Ph.D since 2015 at BCM.

References

  1. 1 2 "Professor Elizabeth Fisher". acmedsci.ac.uk. The Academy of Medical Sciences. Retrieved 13 November 2019.
  2. ↑ Elizabeth Fisher publications from Europe PubMed Central
  3. 1 2 3 4 5 6 7 8 9 "IRIS Prof Elizabeth Fisher". UCL. Retrieved 13 November 2019.
  4. 1 2 "BBC Radio 4 - The Life Scientific, Elizabeth Fisher on chromosomes in mice and men". BBC. Retrieved 13 November 2019.
  5. ↑ Fisher, Elizabeth Mary Claire (1987). Microcloning and molecular mapping of the mouse X chromosome. london.ac.uk (PhD thesis). University of London. hdl:10044/1/66999. OCLC   1103939662. EThOS   uk.bl.ethos.769180. Lock-green.svg
  6. 1 2 UCL (26 September 2019). "prof-elizabeth-fisher-bio". Queen Square Centre for Neuromuscular Diseases. Retrieved 13 November 2019.
  7. ↑ UCL (8 February 2019). "Neuroscience - Elizabeth Fisher". UCL Division of Biosciences. Retrieved 13 November 2019.
  8. ↑ "Meeting the challenges of modelling neurodegenerative disease in mice | Royal Society". royalsociety.org. Retrieved 13 November 2019.
  9. ↑ "Iris View Profile".
  10. ↑ Hafezparast, Majid; et al. (2003). "Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport". Science. 300 (5620): 808–812. doi:10.1126/science.1083129. PMID   12730604. S2CID   40391817.
  11. ↑ "Mouse Models of Neurodegeneration Research". har.mrc.ac.uk. Retrieved 13 November 2019.
  12. 1 2 "Down's syndrome recreated in mice". 22 September 2005. Retrieved 13 November 2019.
  13. ↑ Professor Elizabeth Fisher - Mouse Models of Downs syndrome 2006 , retrieved 13 November 2019
  14. ↑ UCL (8 February 2019). "Neuroscience - Elizabeth Fisher". UCL Division of Biosciences. Retrieved 13 November 2019.
  15. ↑ "Council members | The Academy of Medical Sciences". acmedsci.ac.uk. Retrieved 13 November 2019.
  16. ↑ Fisher, Elizabeth M. C. (1987). "The sex-determining region of the human Y chromosome encodes a finger protein". Cell. 51 (6): 1091–1104. doi:10.1016/0092-8674(87)90595-2. PMID   3690661. S2CID   7454260.
  17. ↑ Fisher, Elizabeth M. C. (2000). "Genealogies of mouse inbred strains". Nature. 24 (1): 23–25. doi:10.1038/71641. PMID   10615122. S2CID   9173641.
  18. ↑ Fisher, Elizabeth M. C. (2005). "Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia". Nature Genetics. 37 (8): 806–808. doi:10.1038/ng1609. PMID   16041373. S2CID   7064719.
  19. ↑ "Elizabeth Fisher | F1000 Faculty Member | F1000Prime". f1000.com. Retrieved 13 November 2019.
  20. ↑ "Prof. Elizabeth Fisher - AcademiaNet". www.academia-net.org. Retrieved 13 November 2019.
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