Investigating research organisms to shed light on human health
From traditional model research organisms like fruit flies to unusual organisms like cavefish, research organisms at the Stowers Institute are carefully chosen to answer a question or help solve a biological mystery.
Discovery made possible through nature
Since the very first cell emerged, life on Earth has evolved in astounding ways. Given the immense diversity of different forms of life, many of the genetic and cellular processes have both evolved and been conserved. Research organisms from single-cell yeasts to highly developed mice can provide clues to the processes governing human health and disease. Here are just a few we study:
Apple snails possess an eye very similar to a human eye that can completely regenerate.
Apple snails are a diverse species of freshwater mollusk found on nearly every continent. While in some cultures, they are considered a culinary delicacy, they are invasive, and voracious, animals that continue to wreak havoc on agricultural and natural wetland ecosystems, after either intentional or accidental introduction. However, they are a unique and valuable research organism for studying evolution and regeneration.
At the Stowers Institute, sealed tightly shut in a lab with extensive precautions taken as to not accidentally introduce the invasive species to the Kansas or Missouri water systems, over 1000 apple snails of species, Pomacea canaliculata, are housed and studied. Due to their long evolutionary history and expansive diversity in morphology, physiology, and geographic distribution, these mollusks are an excellent research organism for studying evolution and comparative genomics. In addition, the eye of the apple snail closely resembles the vertebrate eye. When removed, the snail’s eye regenerates, providing insight into the mechanisms governing eye regeneration of the closest approximation to a human eye found so far.
How the apple snail eye regenerates post-amputation has implications for uncovering the basic mechanisms underpinning regeneration across different species. In humans, damage and disease can lead to irreversible ocular loss of function, or blindness. Remarkably, the eye of the apple snail closely resembles vertebrate eyes. Understanding the ability of apple snail cells to regenerate all eye components—cornea, retina, and lens—in adults and the degree of overlap between this process and embryonic eye development may lead to treatments applicable in humans.
Labs studying apple snails
Cavefish diverged from the river-dwelling fish hundreds of thousands of years ago, and developed adaptive strategies to survive in extreme environments.
Cavefish exist on nearly every continent and reside in underground water systems, most typically in caves that flooded from above ground rivers. Their dark, nutrient-limited environments resulted in genetic adaptations that manifest in both appearance and metabolism.
Cavefish are a unique research organism as independent colonies have developed remarkably similar phenotypic and metabolic adaptations to enable them to survive and thrive in the absence of light and a steady nutrient supply. The Stowers Institute is home to the largest cavefish population in the world collected from underground cave systems in central and east Mexico. The various cavefish populations evolved completely independently from each other yet all display a lack of pigmentation and eyes, a potential energy-saving strategy, and the ability to consume vast quantities of food during periodic nutrient inundation to survive until the next feeding. This feast-or-famine strategy means that these fish have characteristics of obesity and diabetes without any ill effects.
Due to their unique metabolic adaptations that render them immune to any side effects from high body fat and glucose intolerance, cavefish are a powerful research organism for investigating metabolism in other species including humans. Metabolic syndrome can manifest as diabetes, heart disease, and stroke to name a few. Investigating the cellular, molecular, and genetic mechanisms that allow cavefish to remain healthy despite these extreme traits may shed light on potential treatments for metabolic conditions in humans.
Despite their reputation as a nuisance in the kitchen, fruit flies have been a valuable mainstay for biological research for more than 100 years.
The long history of research on fruit flies—and specifically the species Drosophila melanogaster—has generated a deep knowledge base and extensive set of tools and techniques for this research organism. Although they don’t have backbones and look quite dissimilar to humans, their genomes and other fundamental aspects of biology are surprisingly similar.
Fruit fly research has uncovered many key insights into biology across disciplines including genetics, development, neuroscience, evolutionary biology, and behavior. Easily cultured in the lab and able to produce many offspring in a relatively short generation time, fruit flies offer a powerful system for discovering how life works, from the principles of inheritance to how cells, tissues, and organs develop and function.
The emergence of gene and genome sequencing technologies over the past two decades has created an explosion of genomic data available for fruit flies, humans, and many other species. About 75% of known human disease genes have an identifiable match in the fruit fly genome. Fruit fly research has increased our understanding of molecules and mechanisms that become compromised in human health conditions and has uncovered drug targets for treating these conditions. The tractable complexity of fruit flies will continue to allow scientists to explore developmental, behavioral, and evolutionary questions, and relate this insight to other research organisms and humans.
Labs studying fruit flies
Mice are the most common research organism used for studying human disease in the world.
As fellow mammals, mice are very similar genetically and physiologically to humans. Almost all genes in mice have counterparts to genes in humans. This genetic similarity gives rise to many other parallels, such as how we develop from a fertilized egg to an adult and the collection of tissues and organs in our bodies. Our various biological systems – reproductive, digestive, hormonal, and nervous, to name a few – are also very similar to those of mice.
Mouse research enables a broad range of investigation of genes and mechanisms responsible for aspects of development and normal adult biological function, including chromosome integrity, regulation of gene activity, cell division, cell fate and migration, sensory perception, behavioral responses, and aging. The ability to alter the mouse genome using genetic and gene-editing approaches, the ease of inbreeding to generate genetically identical strains, their accelerated lifespan, and decades of prior studies contribute to their prevalence in biological research.
In addition to genetic, developmental, and physiological similarities to humans, mice are also afflicted with many of the same diseases and health conditions such as cancer, hypertension, diabetes, and osteoporosis. Mouse research at Stowers is providing answers to a wide range of biological investigations in areas such as craniofacial and other congenital conditions, body patterning, metabolism, adult stem cell regulation, odor processing, and memory formation.
Labs studying mice
Planarians are wildly diverse flatworms renowned for their astounding regenerative capabilities
Geographically located in almost every corner of the globe, planarians are free-living flatworms that can be found in fresh water, marine environments, and even on land. Hundreds if not thousands of unique strains and species exist and different types can either reproduce asexually and/or sexually.
Planarian research organisms are an exceptional system to uncover cellular and molecular mechanisms underlying regeneration, the replacement of differentiated cells from stem cells following injury or natural physiological turnover. Although certain animals including humans have regenerative capabilities in many tissues and organs, we have limited or no ability to replace missing limbs, or to repair damage to the heart or brain. Insights into the mechanisms governing regeneration are also essential for understanding normal development in higher organisms including humans.
Investigating the remarkable ability of planarian stem cells to differentiate into any and all cells needed for organism regeneration enables identification and characterization of the molecular mechanisms involved. These processes have important and practical applications for understanding normal development, and perhaps to engineer similar mechanistic programs to eventually bypass the need for organ transplantation.
Labs studying planarians
The sea anemone is a marine animal used to study toxin delivery, regeneration, and aging.
The sea anemone, Nematostella vectensis, is a species of cnidarian, a type of water-dwelling sea creature ranging from corals to jellyfish. With an evolutionary history dating back between 500-700 million years, these animals share similar stinging structures used for predation and protection.
Nematostella are excellent research organisms for investigating regeneration, the lack of senescence—the decline in cellular function over time—and their unusual and complex stinging mechanism used to capture prey and to protect themselves from predators. Although sea anemones have been the subject of scientific study for over a century, recent advances in technology have enabled characterization, particularly of their stinging organelles, in spectacular detail.
The structure and mechanism of the cnidarian stinging organelle has incredible applications for designing targeted medical delivery devices for employment at microscopic levels. Additional applications may involve uncovering the mechanisms that underlie Nematostella immortality. Scientists may be able to learn from this cnidarian how to mitigate premature cellular and organ decline in humans.
Labs studying sea anemones
With over 1000 unique yeast species classified, these single-celled eukaryotes are a widely studied microorganism belonging to the fungus kingdom.
The vast variety of yeast species fall into two primary categories: fission and budding yeast. Budding yeast strains have been utilized by humans for thousands of years in culinary and fermented beverage preparation. Fission yeast strains along with budding yeast are exceptional research organisms for studying genetics and reproduction.
The genetic tractability and ease of controlling reproduction cycles in yeast have established these single-celled organisms as an invaluable system for studying genetics and cell life cycles.
With an evolutionary history dating back hundreds of millions of years, different yeast species are staples in research laboratories as well as in baking and brewing. Scientists at the Stowers Institute study and maintain a large variety of natural and lab isolates of both fission and budding yeast, primarily Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. Both types of yeast primarily reproduce asexually, where smaller cells are formed from a mature budding yeast by “budding,” while fission yeast reproduce mitotically through fission, or dividing down the cell’s center to create two identical cells. However, in the lab and in nature, both types can mate and undergo sexual reproduction, typically in nutrient-stressed conditions. In the lab, mating and meiosis can easily be induced to investigate the stages of sexual reproduction and genetic inheritance.
Due to the relative simplicity of their genome, yeasts are some of the most common and powerful research organisms used in the study of genetics and cell biology. The ability to manipulate genes allows investigation of gene expression, transcription and translation, and protein expression and dynamics. In addition, since inducing meiosis is extremely easy, labs at the Institute use yeast to investigate sexual reproduction. The applications for controlling the timing of meiosis have led to breakthroughs in understanding female reproductive aging and the dynamics of how selfish genes can bias transmission of genetic information to offspring, typically at the expense of organism fitness and fertility. These microorganisms have tremendous potential for understanding infertility, aging, and inflammatory diseases in humans.
Zebrafish are freshwater vertebrate animals used to study development, genetics, and regeneration.
The freshwater zebrafish native to South Asia is characterized by lateral line sensory systems. They contain sensory organs called neuromasts dotted along lines on the head and sides of their bodies. Stowers has an extensive collection of zebrafish to accommodate the six labs currently conducting research on these organisms.
Zebrafish are powerful research organisms for investigating a variety of topics. Their embryonic development is extremely rapid and zebrafish larva are transparent which enables visualization of developmental processes. At the embryonic stage, zebrafish heart, lateral line sensory organs and fins regenerate quickly and have enabled Stowers researchers to characterize molecular, cellular, and transcriptional processes at very high spatial and temporal resolution. These mechanisms serve as platforms for studying similar processes in different organs and species.
The many applications of zebrafish research include the mechanisms involved in development, regeneration, genetics, neural crest cells, cancer, and reproduction. For example, the Piotrowski Lab has used the zebrafish lateral line sensory hair cells, named such as they closely resemble the hair cells in the human inner ear, to identify processes involved in repair and regeneration of these cells to address hearing loss in humans. The Trainor lab uses these animals to study neural crest development that can be applied to congenital defects like Treacher-Collins Syndrome.