Gerry Downes

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Gerald "Gerry" Downes is an associate professor in biology at the University of Massachusetts, Amherst. [1] His research expertise is in the genetic requirements for zebrafish swimming. Recently he has expanded his research interests into using the zebrafish system to model idiopathic (unknown cause) epilepsy syndromes.

Contents

Career history

Downes received his bachelor's degree in biology at Johnson C. Smith University in Charlotte, North Carolina, and his PhD in neuroscience with Narasimhan Gautam at Washington University in St. Louis, Missouri. He then moved to Philadelphia and performed a postdoctoral fellowship with Michael Granato at the University of Pennsylvania between 1999 and 2005. He started as an assistant professor of biology at the University of Massachusetts Amherst in 2005, and was promoted to associate professor in 2012.

Research

During his postdoctoral fellowship Downes started to work with the zebrafish ( Danio rerio ) model system. Zebrafish make a great model organism for neuroscience research because they develop quickly and are transparent so their brains and brain development can be easily observed. [2] Furthermore, there are considerable similarity in the genes and pathways involved in brain development between humans and zebrafish. [3] As a postdoctoral fellow, Downes helped develop a method, stochastic labeling, to track the development of individual neurons in intact zebrafish using green fluorescent protein (GFP), which is essential for understanding how neurons grow directionally and form connections in the nervous system. [4] He also started to work on a class of zebrafish mutants that exhibit abnormal swimming behaviors that were isolated from a previous genetic screen. [5] When he started work on this project the identities of the underlying genes weren't known. However, his work showed that mutations in the neurotransmitter-degrading enzyme acetylcholinesterase cause abnormal swimming behavior in one line of mutant zebrafish. [6] In collaboration with John Kuwada's laboratory at the University of Michigan, they also discovered mutations in a zebrafish glycine receptor underlie abnormal swimming in another line of zebrafish [7]

At the University of Massachusetts, Downes continued his work on zebrafish mutants that exhibit abnormal swimming behavior. His group identified mutations in a muscle cell calcium pump critical for muscle relaxation, [8] a mitochondrial enzyme required to break down a subset of amino acids, [9] and a neurotransmitter transporter [10] from three different lines of zebrafish mutants. These zebrafish mutants parallel and serve as new animal models for Brody's Disease, a severe muscle weakness disorder; Maple Syrup Urine Disease, a metabolic disorder that can cause severe neurological damage, [11] and a generalized epilepsy disorder.

Downes is continuing to lead a team of researchers at the University of Massachusetts, who focus on determining the genes and neural networks involved in movement. Downes' laboratory is also working to better understand and developing new treatments for epilepsies. [12]

Related Research Articles

<span class="mw-page-title-main">Zebrafish</span> Species of fish

The zebrafish is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to India and South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio. It is also found in private ponds.

Lafora disease is a rare, adult-onset and autosomal recessive genetic disorder which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of inclusion bodies, known as Lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin. Lafora disease is also a neurodegenerative disease that causes impairment in the development of brain (cerebral) cortical neurons and is a glycogen metabolism disorder.

<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">Notch signaling pathway</span> Series of molecular signals

The Notch signaling pathway is a highly conserved cell signaling system present in most animals. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein. It is a hetero-oligomer composed of a large extracellular portion, which associates in a calcium-dependent, non-covalent interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small intracellular region.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell.

Flamingo is a member of the adhesion-GPCR family of proteins. Flamingo has sequence homology to cadherins and G protein-coupled receptors (GPCR). Flamingo was originally identified as a Drosophila protein involved in planar cell polarity. Mammals have three flamingo homologs, CELSR1, CELSR2, CELSR3. In mice, all three have distinct expression patterns in organs such as the kidney, skin, and lungs, as well as the brain.

Juvenile myoclonic epilepsy (JME), also known as Janz syndrome or impulsive petit mal, is a form of hereditary, idiopathic generalized epilepsy, representing 5–10% of all epilepsy cases. Typically it first presents between the ages of 12 and 18 with myoclonic seizures. These events typically occur after awakening from sleep, during the evening or when sleep-deprived. JME is also characterized by generalized tonic–clonic seizures, and a minority of patients have absence seizures. It was first described by Théodore Herpin in 1857. Understanding of the genetics of JME has been rapidly evolving since the 1990s, and over 20 chromosomal loci and multiple genes have been identified. Given the genetic and clinical heterogeneity of JME some authors have suggested that it should be thought of as a spectrum disorder.

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

A 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial is an enzyme that in humans is encoded by the BCKDHA gene.

<span class="mw-page-title-main">Monocarboxylate transporter 8</span> Protein-coding gene in the species Homo sapiens

Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.

<span class="mw-page-title-main">HAND1</span> Protein-coding gene in the species Homo sapiens

Heart- and neural crest derivatives-expressed protein 1 is a protein that in humans is encoded by the HAND1 gene.

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

Branched chain ketoacid dehydrogenase kinase (BCKDK) is an enzyme encoded by the BCKDK gene on chromosome 16. This enzyme is part of the mitochondrial protein kinases family and it is a regulator of the valine, leucine, and isoleucine catabolic pathways. BCKDK is found in the mitochondrial matrix and the prevalence of it depends on the type of cell. Liver cells tend to have the lowest concentration of BCKDK, whereas skeletal muscle cells have the highest amount. Abnormal activity of this enzyme often leads to diseases such as maple syrup urine disease and cachexia.

<span class="mw-page-title-main">RBFOX1</span> Protein-coding gene in the species Homo sapiens

Fox-1 homolog A, also known as ataxin 2-binding protein 1 (A2BP1) or hexaribonucleotide-binding protein 1 (HRNBP1) or RNA binding protein, fox-1 homolog (Rbfox1), is a protein that in humans is encoded by the RBFOX1 gene.

<span class="mw-page-title-main">Neurogenetics</span> Study of role of genetics in the nervous system

Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.

Nervous system diseases, also known as nervous system or neurological disorders, refers to a small class of medical conditions affecting the nervous system. This category encompasses over 600 different conditions, including genetic disorders, infections, cancer, seizure disorders, conditions with a cardiovascular origin, congenital and developmental disorders, and degenerative disorders.

<span class="mw-page-title-main">Developmental bioelectricity</span> Electric current produced in living cells

Developmental bioelectricity is the regulation of cell, tissue, and organ-level patterning and behavior by electrical signals during the development of embryonic animals and plants. The charge carrier in developmental bioelectricity is the ion rather than the electron, and an electric current and field is generated whenever a net ion flux occurs. Cells and tissues of all types use flows of ions to communicate electrically. Endogenous electric currents and fields, ion fluxes, and differences in resting potential across tissues comprise a signalling system. It functions along with biochemical factors, transcriptional networks, and other physical forces to regulate cell behaviour and large-scale patterning in processes such as embryogenesis, regeneration, and cancer suppression.

Research on amyotrophic lateral sclerosis (ALS) has focused on animal models of the disease, its mechanisms, ways to diagnose and track it, and treatments.

Lauren Orefice is an American neuroscientist and assistant professor in the Department of Molecular Biology at Massachusetts General Hospital and in the Department of Genetics at Harvard Medical School. Orefice has made innovative discoveries about the role of peripheral nerves and sensory hypersensitivity in the development of Autism-like behaviors. Her research now focuses on exploring the basic biology of somatosensory neural circuits for both touch and gastrointestinal function in order to shed light on how peripheral sensation impacts brain development and susceptibility to diseases like Autism Spectrum Disorders.

Michelle Gray is an American neuroscientist and assistant professor of neurology and neurobiology at the University of Alabama Birmingham. Gray is a researcher in the study of the biological basis of Huntington's disease (HD). In her postdoctoral work, she developed a transgenic mouse line, BACHD, that is now used worldwide in the study of HD. Gray's research now focuses on the role of glial cells in HD. In 2020 Gray was named one of the 100 Inspiring Black Scientists in America by Cell Press. She is also a member of the Hereditary Disease Foundation’s scientific board.

Ravi Allada is an Indian-American chronobiologist studying the circadian and homeostatic regulation of sleep primarily in the fruit fly Drosophila. He is currently the Executive Director of the Michigan Neuroscience Institute (MNI), a collective which connects neuroscience investigators across the University of Michigan to probe the mysteries of the brain on a cellular, molecular, and behavioral level. Working with Michael Rosbash, he positionally cloned the Drosophila Clock gene. In his laboratory at Northwestern, he discovered a conserved mechanism for circadian control of sleep-wake cycle, as well as circuit mechanisms that manage levels of sleep.

Makoto Furutani-Seiki is a Japanese molecular biologist who is a Professor of Systems Biochemistry in the School of Medicine at Yamaguchi University, Japan.

References

  1. "UMass Amherst: Biology Department: Faculty: Gerald B. Downes". www.bio.umass.edu. September 28, 2009. Retrieved June 28, 2021.
  2. Burke, Elizabeth (August 8, 2016). "Why Use Zebrafish to Study Human Diseases?". NIH Intramural Research Program. Retrieved September 19, 2020.
  3. Monesson-Olson, Bryan; McClain, Jon J.; Case, Abigail E.; Dorman, Hanna E.; Turkewitz, Daniel R.; Steiner, Aaron B.; Downes, Gerald B. (2018). "Expression of the eight GABAA receptor α subunits in the developing zebrafish central nervous system". PLOS ONE. 13 (4): e0196083. Bibcode:2018PLoSO..1396083M. doi: 10.1371/journal.pone.0196083 . ISSN   1932-6203. PMC   5922542 . PMID   29702678.
  4. Downes, Gerald B.; Waterbury, Julie A.; Granato, Michael (November 2002). "Rapid in vivo labeling of identified zebrafish neurons". Genesis. 34 (3): 196–202. doi:10.1002/gene.10120. ISSN   1526-954X. PMID   12395384. S2CID   8656186.
  5. Nüsslein-Volhard, Christiane (November 2012). "The zebrafish issue of Development". Development. 139 (22): 4099–4103. doi: 10.1242/dev.085217 . ISSN   1477-9129. PMID   23093421. S2CID   7854819.
  6. Downes, Gerald B.; Granato, Michael (June 1, 2004). "Acetylcholinesterase function is dispensable for sensory neurite growth but is critical for neuromuscular synapse stability". Developmental Biology. 270 (1): 232–245. doi: 10.1016/j.ydbio.2004.02.027 . ISSN   0012-1606. PMID   15136152.
  7. Hirata, Hiromi; Saint-Amant, Louis; Downes, Gerald B.; Cui, Wilson W.; Zhou, Weibin; Granato, Michael; Kuwada, John Y. (June 7, 2005). "Zebrafish bandoneon mutants display behavioral defects due to a mutation in the glycine receptor beta-subunit". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8345–8350. Bibcode:2005PNAS..102.8345H. doi: 10.1073/pnas.0500862102 . ISSN   0027-8424. PMC   1149420 . PMID   15928085.
  8. Olson, Bryan D.; Sgourdou, Paraskevi; Downes, Gerald B. (June 2010). "Analysis of a zebrafish behavioral mutant reveals a dominant mutation in atp2a1/SERCA1". Genesis. 48 (6): 354–361. doi:10.1002/dvg.20631. ISSN   1526-968X. PMC   2885577 . PMID   20533403.
  9. Friedrich, Timo; Lambert, Aaron M.; Masino, Mark A.; Downes, Gerald B. (March 2012). "Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease". Disease Models & Mechanisms. 5 (2): 248–258. doi:10.1242/dmm.008383. ISSN   1754-8411. PMC   3291646 . PMID   22046030.
  10. McKeown, Kelly Anne; Moreno, Rosa; Hall, Victoria L.; Ribera, Angeles B.; Downes, Gerald B. (February 15, 2012). "Disruption of Eaat2b, a glutamate transporter, results in abnormal motor behaviors in developing zebrafish". Developmental Biology. 362 (2): 162–171. doi:10.1016/j.ydbio.2011.11.001. ISSN   1095-564X. PMC   4013685 . PMID   22094018.
  11. Roberts, Nathan B. (July 2012). "Maple syrup urine disease: new insights from a zebrafish model". Disease Models & Mechanisms. 5 (4): 417–418. doi:10.1242/dmm.010272. ISSN   1754-8411. PMC   3380704 . PMID   22730471.
  12. "Research". Downes Laboratory. UMass Amherst.