Biology’s Next Top Model: Zebrafish – The Varsity
It is not a hybrid of a zebra and a fish; rather, Danio rerio, commonly known as zebrafish, is a small freshwater fish found in tropical climates. The zebrafish is characterized by its slender body and shiny stripes, and is well known for its unique biological properties – properties that have made it a favored organism for modeling research in genetics, embryological development, and medicine.
“Model organisms” like zebrafish are particularly important for scientists and researchers to learn and discover the mechanisms of biological processes.
The History of Zebrafish as a Model Organism
In the 1960s, zebrafish began to be used as a model organism in various biological studies. Their small size, low-maintenance care needs, short prenatal period, and other unique characteristics make them ideal candidates for research.
Zebrafish eggs develop outside the mother’s body. Since the embryos are transparent, it is possible to easily observe the early embryological developments of zebrafish and the sequential growth of their internal structures. Zebrafish are very similar to mammals in terms of important anatomical and physiological features. Classified as vertebrates, they also share a remarkable number of similarities with humans in particular – they have the same major tissue systems and organs as us, and share many common characteristics with the muscles, blood, kidneys and eyes of humans. , specifically.
These commonalities are also present at the genetic level: zebrafish and humans share about 70% of their genes. Eighty-four percent of genes linked to human diseases have a close match with their zebrafish counterparts. Research done with zebrafish as a model organism therefore has great potential to unlock new avenues for medicine and the resolution of human disease, allowing us to better understand the molecular mechanisms behind how and why we get sick.
The genetics of zebrafish
Advances in genetic engineering technology and new zebrafish facilities at many institutions around the world have allowed zebrafish to become a widely used model in genetic studies. The zebrafish is the favored organism for this area of research due to their easily accessible genes, low cost of providing them, and fewer ethical restrictions on research on zebrafish compared to mammalian organisms. Over the past few decades, zebrafish have been used in both forward and reverse genetic screens, with very impactful results.
“Direct genetics” involves looking at the genetic cause of a mutation, which helps scientists identify a number of different variations of the same gene. In the 1990s, a group of scientists attempted to identify many genes critical to organ system development by mass screening zebrafish. It was the first time that scientists had done this type of screening on a vertebrate species, and it has yielded much more information about the genetic causes of different diseases. The screening identified 1,500 mutations in 400 different genes responsible for developmental defects through observation, which was made possible by the fact that zebrafish embryos are nearly transparent and develop very quickly.
“Reverse genetics” consists of modifying a particular gene of interest and observing the consequences. Although rodents are the usual model organism for reverse genetics studies, they require scientists to inject target genes into unfertilized eggs, which can be difficult. It is therefore much easier to conduct reverse genetic analyzes in embryonic and larval zebrafish.
Early zebrafish embryos can be injected with genetic material so scientists can observe if there is a temporary change in how the target gene is expressed, or if there is an absence of genetic response. This method allows researchers to study early zebrafish development in a way that allows for close examination of how genes affect an organism at a place and time in the developmental process that researchers choose. This disease modeling is how scientists search for effective therapies for certain genetic conditions.
Researchers generally have an easier time performing these forward and reverse genetic analyzes on zebrafish larvae than on some other animals, giving zebrafish a distinct advantage. The genetic research we have been able to conduct on zebrafish has allowed us to model and better understand some of the most widespread and dangerous diseases of our time, such as cancer.
The regenerative abilities of zebrafish
To learn more about using zebrafish as a model organism, the university interviewed Ian Scott, professor of molecular genetics at U of T and principal investigator at the SickKids Foundation. Scott has been conducting research using zebrafish as a model organism for years.
Scott spoke about the species’ incredible regenerative abilities, explaining that zebrafish are able to repair or regrow many parts of their body if injured, including severed spinal cords and damaged hearts. Although the mechanisms driving these regenerative processes are not yet fully understood, we do know that they involve cells entering a different state where they are able to undergo the necessary transformations. Scott thinks that in the distant future, it might be possible to activate these same types of regenerative processes in people who have suffered serious injuries.
Professor Ashley Bruce from the Department of Cellular and Systems Biology at the University of Toronto, who is also an expert in embryonic development, wrote to the university in an email that this line of research has long-term potential for health care. Bruce added that, in situations such as the aftermath of a heart attack, it could be used to develop “approaches in humans to stimulate cardiac regeneration”.
How zebrafish help drug discovery
Ultimately, the goal of disease modeling is to improve existing diagnostic methods and therapies by developing new drugs to treat different conditions. To this end, the zebrafish also serves as an ideal model for testing libraries of chemical molecules in search of new drugs to treat genetic diseases.
In the context of pharmacology, it is necessary to observe physiological changes in living organisms – instead of stem cells – to accurately assess the amount of administered chemicals able to act and whether they have potential adverse effects. . Intact animal models are particularly important in neuroscience drug discovery. Due to the complexity of how the nervous system works, even undifferentiated stem cells obtained from patients are not as well suited for drug discovery as fully intact organisms like zebrafish.
Most zebrafish organs have similar physiological functions to corresponding human organs. There are even some characteristics where zebrafish physiology more closely resembles humans than rodent models, namely the electrical properties of heart cells. According to a Nature article, zebrafish larvae are known to have “[a] functional liver, kidneys, and blood-brain barriers,” which shed light on how zebrafish respond early in development to chemicals administered by scientists.
Promising chemical compounds tested in zebrafish are also directly transferable to other mammalian model organisms without significant pharmacological modifications. Although, when tested in zebrafish, some chemical compounds may not display all of the pharmacological properties we need to observe, the dose-response relationships obtained from observing zebrafish still serve as valuable references that indicate a direction for future drug development.
Foreseeable challenges and opportunities for zebrafish
Despite promising prospects for drug discovery and disease modeling using zebrafish, scientists face many challenges in the field.
Researchers have yet to determine the details of how different “behavioral phenotypes” map to potential therapies. In order to standardize behavioral responses to chemical compounds in humans, it is necessary to carefully examine the behaviors induced by new chemical compounds. This large-scale undertaking requires not only scientific expertise, but also a substantial increase in financial investment.
Rapid advances in genome engineering and genome editing technology will most likely facilitate the reconstruction of many human genetic mutations in zebrafish models. Currently, chemical screens have demonstrated the utility of zebrafish in identifying compounds capable of counteracting pathogenic genetic mutations.
Regardless of all the challenges that genetic research may face in the future, there is no doubt that the zebrafish is one of the emerging biological supermodels of our time.