Presidential Early Career Award for Scientists and Engineers (PECASE), The American Academy of Arts and Sciences, National Medal of Technology & Innovation, Samuel J. Heyman Service to America Medals, Advancing Computational and Structural Biology, Uncovering New Opportunities for Natural Products, Unlocking the Potential of RNA Biology and Therapeutics, Chief, Radiation Epidemiology Branch, NCI, Earl Stadtman Investigator Frequently Asked Questions, 70% of human genes are found in zebrafish, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484855/, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545/, Little Fish in a Big Pond Reveal New Answers to Old Questions, African Ancestry May Influence Immune Response to Prostate Cancer, Three-Minute Talks Showcase Smooth-Talking Scientists, Overturning the Orthodoxy About the Brains Stress Chemical. PubMed Central https://doi.org/10.1111/j.1365-2567.2010.03358.x. CAS Fish Shellfish Immunol. October. Arch Med Vet. Lab Anim. Zebrafish also presents the enzyme system involved in the process of genetic rearrangement that originates the B (BCR) and T (TCR) lymphocyte receptors. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. One of the most important pathogen studies applied to fishing production is attributed to Guo et al. Microb Pathog. Brudal E, Ulanova LS, Lampe EO, Rishovd AL, Griffiths G, Winther-Larsen HC. Open survey, Tiny fish, big splash: the story of the zebrafish. Trends Microbiol. Dev Comp Immunol. It has been shown to be efficient in preventing disseminated forms of tuberculosis in children; however, its efficiency is limited in areas where individuals have had prior exposure to environmental mycobacteria, and its efficacy decreased with a hosts age [55]. It presents numerous advantages of this type of animal model in tests of efficacy and safety of both animal and human vaccines, thus highlighting gains in time and cost reduction of research and analyzes. Find more COVID-19 testing locations on Maryland.gov. Front Microbiol. Palha N, Guivel-Benhassine F, Briolat V, Lutfalla G, Sourisseau M, Ellett F, et al. Liu X, Wu H, Liu Q, Wang Q, Xiao J, Chang X, et al. Aquac Res. Miller JD, Neely MN. https://doi.org/10.1016/j.fsi.2017.06.015. McCallion and his lab team dig deep into genetic codes that control when and where genes are switched on/off, combining cutting-edge genomic tools and computational artificial intelligence to find the abnormalities that can influence diseases such as Parkinsons. For high transfer rate, the microbes can be readily injected into the yolk for the first few hours after fertilization. Scientists are working to find out the specific factors involved in this process to see if this will help us to develop ways of repairing the heart in humans with heart failure or who have suffered heart attacks. In Mumms work studying degenerative eye disease, he takes advantage of the fact that humans and zebrafish share a trait a specific cell type that can revert to being a stem cell that allows them to produce new cells in response to injury or disease in the retina. Curr Protoc Toxicol. Significant factors contributing to this success are external fertilization and transparent embryos, which allow scientists to observe growth and possible mutations in developing zebrafish; fluorescent dyes mark transgenic organs/tissues and make them easier to identify. Moreover, zebrafish have two eyes, a mouth, brain, spinal cord, intestine, pancreas, liver, bile ducts, kidney, esophagus, heart, ear, nose, muscle, blood, bone, cartilage, and teeth. A model organism is a species that has been widely studied, usually because it is easy to maintain and breed in a laboratory setting and has particular experimental advantages. 2013;10(2):1948. 2019;94:35572. 15, 2014;7(11):122737. Google Scholar. Expert Committee on Biological Standardisation. This model is an important tool for the development of new safe vaccines against diseases which do not yet have preventive treatment, or for which the existing vaccines are not so effective. https://doi.org/10.1016/j.vetimm.2016.01.004. 2011;6(8):e22921. Nat Rev Genet. While use of zebrafish as models began in the 1960s, they swam to prominence in the 1990s and 2000s after a discovery related to gene mutation. Thus, the Zebrafish model has the advantage of a researcher to follow in real-time the fishs development from its embryogenesis to full organ development which is reached about 36h after fertilization. Cheng T, Kam JY, Johansen MD, Oehlers SH. Emerg Microbes Infect. The one-cell-stage fertilized eggs can be easily injected with DNA or RNA to permanently modify their genetic makeup in order to generate transgenic or knock-out zebrafish lines. Alternatively, a more localized infection may be induced by the injection of microbes into the muscle tail or the hindbrain ventricle [6]. https://doi.org/10.1016/j.tim.2014.02.002. The use of the Zebrafish model for the production of vaccines with application for both animals and humans, despite already being a reality, is still underused. 2015;6(5):e0142515. The fish have helped investigators at Johns Hopkins make important breakthroughs toward regenerating eye tissue, understanding thyroid cancer and making sense of the DNA tangles that regulate cell activity. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. That amounts to a whole lot of time and money saved., of the Institute for Basic Biomedical Sciences. It has recently been shown that zebrafish can also be used for the potential screening of DNA-based vaccines and, in particular, for identifying novel antigens protecting against mycobacteria [67]. Zebrafish embryos are also laid and fertilized externally, which allows them to be easily manipulated in a variety of ways. The name zebrafish comes from the horizontal blue stripes on each side of their bodies. 2015;82(3):17483. Every blood vessel in a living zebrafish embryo can be seen using just a low-power microscope. Moreover, the mortality and clinical signs as well as laboratory tests are usually analyzed to evaluate the innate (non-specific) or adaptive (specific) immune system response. https://doi.org/10.1111/jam.13002. Thus, using the zebrafish model, it is possible to replace and reduce the use of mammals in research as well as mitigate problems related to the welfare of those animals. Brudal E, Lampe EO, Reubsaet L, Roos N, Hegna IK, Thrane IM, et al. Zhang et al. Since the 1960s, the zebrafish (Danio rerio) has becomeincreasingly important to scientific research.It has many characteristics that make it a valuable model for studying human genetics anddisease. Although these risks are irrelevant when compared to damages that could be caused by the non-use of a vaccine, the toxicology, the side effects and immunization at different concentrations ought to be adequately tested. Rocker AJ, Weiss AR, Lam JS, Van Raay TJ, Khursigara CM. 2012;61:e3781. Tandberg J, Oliver C, Lagos L, Gaarder M, Yez AJ, Ropstad E, Winther-Larsen HC. The Center for Functional Investigation in Zebrafish or the FINZ center is a research core facility of the McKusick-Nathans Institute of Genetic Medicine. 22, 2007;8(5):353. https://doi.org/10.1038/nrg2091. Their transparency also enables the visualization of fluorescently labeled tissues in transgenic zebrafish embryos. We needed a way to test hundreds and hundreds of these things. Duggan GM, Mostowy S. Use of zebrafish to study Shigella infection. Chemosphere. https://doi.org/10.1038/s41684-019-0397-4. The researchers introduce various drug compounds to the water and study the results. Fukushima HCS, Leal CAG, Cavalcante RB, Figueiredo HCP, Arijo S, Moriigo MA, et al. Zebrafish have played a key role in Prescotts pursuit of pharmaceutical breakthroughs to combat thyroid cancer. Therefore, the body is able to produce antibodies that recognize, signal and neutralize pathogens or particular cellular responses which detect the specific antigens with high efficiency and affinity. The authors declare that they have no competing interests. It reduces the contamination of water bodies by the excessive use of antibiotics, and the reduction of final fish product quality [5, 24, 42, 79, 100]. https://doi.org/10.1242/dmm.032151. Overall more affordable to house and maintain. Saralahti A. In spite of rodents being the most widely used research model in the world, in recent decades the use of the zebrafish (Danio rerio) model has exponentially increased among the scientific community. The fish also allow for fast and efficient testing of drugs to combat disease. Identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (Danio rerio). OECD. J Fish Dis. Google Scholar. Incidentally, scientists found zebrafish to share 70% of the genetic makeup of humans. Regarding the administration of vaccines, in view of the different routes of applications presented in animals and humans, the zebrafish model still allows the immunization of embryos, facilitated by its transparency, using glass needles (Figs.3 and 4). https://doi.org/10.1016/j.actatropica.2003.10.020. [86], zebrafish can be also used as a model for pathogenesis and host defense, modeling many human diseases, such as tuberculosis, Staphylococcus aureus and Shigella infection, among others, as well as model to investigate immune cells, infection and inflammation of different kind of human diseases. Grow extremely fast, up to 30 times the rate of human embryos. Somewhere along the way in their evolutionary selection, zebrafish developed the capacity for self-repair, says Mumm. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Let me explain. 2018;82:509. I want to know whats so special that allows them to do this. This model has the advantage of having OECD-specific guidelines for safety evaluation of chemical compounds (acute toxicity), which is performed within 96h [65]. Contrasted innate responses to two viruses in zebrafish: insights into the ancestral repertoire of vertebrate IFN-stimulated genes. [58] testing the protective efficacy of Streptococcus iniae derived enolase against Streptococcal infection in zebrafish model. Furthermore, it serves well to test new therapeutic agents, such as the safety of new vaccines. Zebrafish have a similar genetic structure to humans. JoVE (J Vis Exp). https://doi.org/10.1016/j.micinf.2008.07.016. We could see sequences that stood out as highly similar among different species, but we didnt have a large-scale, genomewide way to test our hypotheses, McCallion recalls. Their muscle, blood, kidney and eyes share many features with human systems. And zebrafish continue to deliver according to Dr Derek Stemple, from the Wellcome Trust Sanger Institute: "This genome will help to uncover the biological processes responsible for common and rare diseases and opens up exciting new avenues for disease screening and drug development.". Moreover, Brudal et al. https://doi.org/10.1016/j.vaccine.2006.05.015. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545/. Cite this article. The study of the use of vaccines in fish is an area of fast-growing. Chen H, Zhang L, Li S, Ling K, Chen X, Lin C. CpG-ODN 2007 protects zebrafish against Vibrio vulnificus-induced infection. Practically speaking they offer many advantages as research models: The understanding of several human diseases has already grown leaps and bounds because of zebrafish studies. Moreover, teleost models offer an expanding platform for the understanding of mycobacterial infections and those mechanisms that offer the greatest potential to enhance host protection [37]. Vaccine. Bailone RL, Fukushima H, Roa R, Corra T, Janke H, Setti P, et al. Torraca et al. Sullivan C, Matty MA, Jurczyszak D, Gabor KA, Millard PJ, Tobin DM, Kim CH. Identification of novel immunogenic proteins against Streptococcus parauberis in a zebrafish model by reverse vaccinology. McCallion, who co-directs the FINZ center, and Fisher, now a faculty member at Boston University, convinced medical school leadership that zebrafish would offer a more efficient, less expensive way to do genetics research. Infect Immun. 2016;34(42):5099106. 2016. They can regrow pancreatic beta cells, she says, referring to the cells that store and release insulin. 2016;47(11):366778. Benard EL, Van der Sar AM, Ellett F, Lieschke GJ, Spaink HP, Meijer AH. Cryptococcus neoformans intracellular proliferation and capsule size determines early macrophage control of infection. In the case of vaccine against poliomyelitis, vaccine contagion happened to 1 in every 3.6 million vaccinated. [11] observed that vaccination with outer membrane vesicles from F. noatunensis reduced the development of francisellosis in a zebrafish model. Embryos of zebrafish 0, 6, 24 and 48h post-fertilization. Ding C, Liu Q, Li J, Ma J, Wang S, Dong Q, et al. https://doi.org/10.1016/j.stem.2007.11.002. Consequently, the presence in fish of elements of innate and adaptive immunity enables research in infectious processes, being susceptible to infections by gram-negative and gram-positive bacteria, protozoa, viruses, fungi and mycobacteria. Vibrio vulnificus, that is an aquatic pathogen that can cause primary sepsis and soft tissue infection, was also tested during an experimentation of zebrafishs reaction to vaccine. Then they observe the fish to learn the cancerous cells origins and how they replicate. Initially, 99 publications were identified which included books, rulings and articles published by international scientific journals of high impact factor. As aquaculture expands and the need to control pathogens becomes more pressing, the commercial vaccination of different varieties of fish is already a reality in many countries. He says the fish are speeding up the process by helping eliminate the scientific dead ends faster than ever before. 2011;10(7):93244. It was concluded that CpG oligodeoxynucleotides, a type of essential immunomodulators, protected zebrafish against Vibrio vulnificus induced infection [15]. A review of the literature was carried out aiming at presenting the most recent information on vaccination of fish, which brings to light the advantages of this animal model in tests of efficacy and safety of both animal and human vaccines. This is only one step in a complicated process, however: morphological changes and overexpressed fluorescent proteins in organs could be observed in the transparent embryos, but their effect on genes could not. Rev Educ Cont Med Vet e Zoo CRMV-SP. Manage cookies/Do not sell my data we use in the preference centre. Clin Pharm Ther. https://doi.org/10.1016/j.fsi.2014.10.025. Commercial mutant zebrafish lines and the recently developed CRISPR/Cas9 genome modification system provide the means to create knockout zebrafish for studying individual genes at a whole organism level [66]. Zhang H, Shen B, Wu H, Gao L, Liu Q, Wang Q, et al. Due to the quality of the sequencing, scientists have successfully developed nearly 15,000 mutations in zebrafish models. Vaccine. [101] studied Th17-like immune response in fish mucosal tissues after administration of live attenuated V. anguillarum via different vaccination routes. For us, the new cells become scar tissue. Dev Comp Immunol. 2015;8(11):137588. Int J Mol Sci. https://doi.org/10.1111/j.1651-2227.2012.02835.x. J Fish Dis. Toh MC, Goodyear M, Daigneault M, Allen-Vercoe E, Van Raay TJ. 1996;6(4):4618. Tenor JL, Oehlers SH, Yang JL, Tobin DM, Perfect JR. Live imaging of host-parasite interactions in a zebrafish infection model reveals cryptococcal determinants of virulence and central nervous system invasion. In addition, observations can be made in real-time allowing for the monitoring of embryogenesis (Fig.1) as well as regarding the effects of vaccines in relation to cardiovascular, hepatic, nervous, and endocrine, not to mention, behavioral aspects too [18, 40]. Taking a gene from jellyfish that enables their incandescent glow, the FINZ team introduces that gene into a zebrafish, lighting up the liver and allowing researchers to observe its growth and function. https://doi.org/10.1016/j.dci.2015.12.016. As a result, vaccines protect the body against future infections [27] thus reducing the need for the use of antibiotics and other types of drugs. Annually about two million people perish of tuberculosis and, so far, due to the lack of well-established animal models, such a disease has been difficult to study [51]. 2016;120(2):44151. In addition to their genetic similarity to humans, zebrafish have other attributes that make them attractive to scientists who need to research large numbers of the same organism. https://doi.org/10.1080/08905436.2019.1673173. Marianes AE, Zimmerman AM. How has the site influenced you (or others)? Fish Shellfish Immunol. 2021, Oct Status of vaccine research and development for Shigella. 2015;35(3):7917. To keep the embryos alive after fertilizing or injecting them, they would need to be transplanted into another female mouse, as well. Guo Z, Lin Y, Wang X, Fu Y, Lin W, Lin X. In this article well describe how the zebrafish genome compares to humans, and how these similarities benefit disease research. Zebrafish as a novel model for non-typhoidal salmonella pathogenesis, transmission and vaccine efficacy. The publications were selected according to relevance and timeliness. Yet as we all know, looks can be deceiving. Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract. 2019:780742. https://doi.org/10.1101/780742. Fish Shellfish Immu. A robust human norovirus replication model in zebrafish larvae. Similarly, this model also helps to elucidate bacterial infections in animals and humans by Aeromonas hydrophila [91], Pseudomonas aeruginosa [74], Escherichia coli nonpathogenic [63], E. coli CFT073 [95], Listeria monocytogenes [80, 81], Myroides odoratimimus [72], Cronobacter turicensis [25], Streptococcus agalactiae [70, 96], Streptococcus iniae and Streptococcus pyogenes [59, 76, 77], among others [12, 85]. 2015; https://super.abril.com.br/saude/os-riscos-reais-da-vacina/ Accessed 27 Feb 2020. California Privacy Statement, https://doi.org/10.1089/zeb.2012.0814. 2018;11(3):dmm033175. Laboratory Animal Research https://doi.org/10.1128/IAI.00077-14. Fish Shellfish Immunol. What is the first part of your school's postcode? https://doi.org/10.1371/journal.ppat.1008009. For instance, a researcher wanting to study how the liver develops and functions can ask the FINZ center to produce zebrafish with glowing livers. Kavaliauskis A, Arnemo M, Speth M, Lagos L, Rishovd AL, Estepa A, et al. Zebrafish also have chromosomal regions which influence sex determination, another characteristic unique to the species. Because their genetic profile is remarkably similar to our own, zebrafish are also found in the Miller Research Building on the medical campus of The Johns Hopkins University, where they provide scientists with genetic clues to medical mysteries. Guo et al. In order to improve protection, vaccination is used to boost immunity against diseases caused by microorganisms. Zebrafish as an animal model for food safety research: trends in the animal research. The Zebrafish model has been widely used in both animal and human health research and, more recently, in aquaculture too. Fehr A, Eshwar AK, Neuhauss SC, Ruetten M, Lehner A, Vaughan L. Evaluation of zebrafish as a model to study the pathogenesis of the opportunistic pathogen Cronobacter turicensis. Additionally, zebrafish are not useful models for human diseases that mainly take place in a tissue type or body part that zebrafish do not have (e.g., prostate, mammary glands, lungs). Reproduce every 10 days and lay 200 to 300 eggs per couple. Biological breakthroughs in cancer and heart disease research have been especially promising. 2019;48(10):2847. Only two other genomes have been sequenced to such a high level: the mouse and the human genomes. For a fee, FINZ offers numerous genetic services to colleagues throughout the institution, including modifying the genome to produce fish with traits that researchers want to study. 2018;15(2):124e132. Advanced developments in fish vaccination. This article first appeared in Dome (May 2018). Yet, despite there not existing vaccine available as yet, the human and animal challengerechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas are promising. 2008;10(9):105762. Lohi O, Parikka M, Rmet M. The zebrafish as a model for paediatric diseases. Acta Trop. They grow at an extremely fast rate, developing as much in a day as a human embryo develops in one month. The generation of a knock-out of the dystrophin gene in zebrafish has been shown to closely resemble the severity and progression of the human disease Duchenne muscular dystrophy. In recent years, zebrafish models have been chosen as the preferred model in the production of fish vaccination experiments against several pathogens that cause losses in aquaculture around the world such as bacteriosis and viruses. If you have any other comments or suggestions, please let us know at comment@yourgenome.org, Can you spare 5-8 minutes to tell us what you think of this website? The incidence of the disease decreased following Shigellas infection which pointsto a biological feasibility of a vaccine [54]. Mani S, Wierzba T, Walker RI. Dev Comp Immunol. MBio. Int J Mol Sci. When compared to injection vaccination, immersion vaccination elicited intense Th17-like immune responses in the gut tissue of zebrafish. Therefore, zebrafish constitutes an excellent experimental model for behavioral, genetic and toxicological studies which unravels the mechanism of various human diseases. They observed that the immune response was increased after vaccination. M. bovis is most common in cattle, but also affects humans. Human melanoma has also been successfully modeled in zebrafish. Kari G, Rodeck U, Dicker AP. Bernut A, Dupont C, Sahuquet A, Herrmann JL, Lutfalla G, Kremer L. Deciphering and imaging pathogenesis and cording of Mycobacterium abscessus in zebrafish embryos. Thus both species have the capacity to produce new cells to heal the eye. And since zebrafish embryos are translucent, scientists can observe their development in real time, watching organs and whole systems grow from stem cells. Shahin K, Shinn AP, Metselaar M, Ramirez-Paredes JG, Monaghan SJ, Thompson KD, et al. The most commonly identified mutation in human melanomasa single amino acid change in the gene BRAFwas created in zebrafish to make a knock-in model. 2015;88:228. The importance of the p53 gene in human carcinogenesis is well recognized and recent studies have shown zebrafish as an excellent model for assessing the presence (or not) of gene stability. https://doi.org/10.1128/EC.05005-11. PubMed Eukaryot Cell. Kim et al. https://doi.org/10.1016/j.antiviral.2016.12.013. Nat Rev Drug Discov. May 2018From floor to ceiling, in row after row of small, bubbling tanks, 30,000 tiny tropical fish are unlocking the secrets to diseases that have vexed generations of researchers and physicians. https://doi.org/10.1111/sji.12320. Which of these best describes your occupation? PLoS One. https://doi.org/10.1371/journal.pone.0181942. Howlader et al. Mumm says that, while science has focused on mice as models to study disease since the creation of the first genetically altered mouse in 1980, zebrafish have, in recent years, emerged as an important model species as well. Larvae of zebrafish 72 and 96h post-fertilization. 2004;91(1):5368. 2014;192(9):432841. The zebrafish genome has been fully sequenced to a very high quality. Human challenge trials for vaccine development: regulatory considerations. Bailone (Mean author); Fukushima (Zebrafish review); Fernandes (Photographies); Aguiar (Translator); Corra, Junke and Setti (Bibliographic review help, vaccine review, team group of Laboratory of Applied Immunology); Roa (Bailones Supervisor, review final corrections); Borra (Bailones Co-supervisor, review final corrections). Thirty different cores from departments across The Johns Hopkins University offer more than 500 different research-related services. An adult zebrafish model for preclinical tuberculosis vaccine development. Membrane vesicles from Piscirickettsia salmonis induce protective immunity and reduce development of salmonid rickettsial septicemia in an adult zebrafish model. Hematology and agglutination titer after polyvalent immunization and subsequent challenge with Aeromonas hydrophila in Nile tilapia (Oreochromis niloticus). Yet, the usefulness of this model is not limited to tuberculosis, which as seen before it could benefit research for many other important infectious diseases [51]. However, there is a limit on what types of diseases can be studied in zebrafish. Gabor KA, Goody MF, Mowel WK, Breitbach ME, Gratacap RL, Witten PE, et al. When another commonly observed melanoma mutation of the gene SETDB1 was added to the BRAF knock-in zebrafish, a melanoma rapidly developed. Zebrafish play an important role in research at Johns Hopkins. Zebrafish as tools for drug discovery. 2018;36(30):444753. Their quick growth, transparent embryos and, most importantly, genetic makeup, combine to make zebrafish an ideal model for research. 2015;4(1):19. [50] analyzed the profiling immune response in zebrafish intestine, skin, spleen and kidney when immersion vaccinated was used with a live attenuated V. anguillarum vaccine. Zebrafish produce hundreds of offspring at weekly intervals providing scientists with an ample supply of. 2020. p. 126288. b Female. Furthermore, Liu et al. The zebrafish is about 2.5 cm to 4 cm long. Hodgkinson JW, Belosevic M, Elks PM, Barreda DR. Teleost contributions to the understanding of mycobacterial diseases. Zebrafish may seem a strange model for research related to humanstheyre not mammals, they have no arms or legs, they have different breathing systems, they live underwater, etc. Research in tumor suppressor genes p53 and apc (adenomatous polyposis coli) is another area of great interest. Uso de vacinas na piscicultura: verdades, mitos e perspectivas. 2016;170:259. This is because such a small tropical freshwater teleost fish has crucial genetic, anatomical and physiological homology with mammals. Cell Stem Cell. Panorama da Aquicultura. In addition, it should be noted the role vaccines play in controlling diseases as preventative as well as non-therapeutic measures. He says that, while that work remains arduous, early in his career it was far more difficult.
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