Zebrafish are genetically similar to humans and are good models for human biology and disease. Now, researchers at Children's Hospital Boston have created a zebrafish that is transparent throughout its life. The new fish allows scientists to directly view its internal organs, and observe processes like tumor metastasis and blood production after bone-marrow transplant in a living organism.
Caption: The transparent zebrafish.
Credit: Richard Whtie, MD, PhD
The fish, described in the February 7 issue of Cell Stem Cell, was created by Richard White, MD, PhD, a clinical fellow in the Stem Cell Program at Children's, with others in the laboratory of Leonard Zon, PhD.
The classic method for studying human diseases in animals is to allow the animal to get the disease, kill and dissect the animal, then ask, "what happened?" But in cancer and other fast-changing processes that traverse the body, this method is bound to miss something. "It's like taking a photograph when you need a video," says White, also an instructor of medicine at the Dana-Farber Cancer Institute.
Zebrafish embryos have enabled researchers to study disease in live organisms, since they are transparent. But zebrafish adults are opaque. "Everything after four weeks has been invisible to us," says White.
White's first experiment on the zebrafish examined how a cancer spreads. "The process by which a tumor goes from being localized to widespread and ultimately fatal is the most vexing problem that oncologists face," says White. "We don't know why cancer cells decide to move away from their primary site to other parts in the body."
White created a fluorescent melanoma tumor in the transparent fish's abdominal cavity. Viewing the fish under a microscope, White saw the cancer cells begin to spread within five days. He even saw individual cells metastasize, something that has not been observed, so readily and in real-time, in a living organism.
The spreading melanoma cells appeared to "home" to the skin after leaving the abdominal cavity. "This told us that when tumor cells spread to other parts in the body, they don't do it randomly," says White. "They know where to go."
White plans to study tumor cell homing, then look for ways to modify the tumor cells or cells of the host so that the spreading cells never find their new location.
The fish may also answer questions about stem cell transplants. While transplants of blood-forming stem cells help cancer patients rebuild healthy blood, some transplants don't "take," for reasons that are unknown. Scientists have lacked a full understanding what steps blood stem cells must take to do their job, says White.
White showed the process is observable in the fish. He first irradiated a transparent fish's bone marrow, then transplanted fluorescent blood-forming stem cells from another zebrafish. By four weeks, the fluorescent stem cells had visibly migrated and grown in the fish's bone marrow, which is in the kidney. Even individual stem cells were visible, something researchers haven't easily observed in a living organism, White says.
By studying how the stem cells embed and build blood in the fish, scientists can look for ways to help patients rebuild their blood faster. Drugs and genes could be tested in the living fish, with direct observation of results, White says.
White created the transparent fish simply by mating two existing zebrafish breeds. Zebrafish have three pigments in their skin—reflective, black, and yellow. White mated a breed that lacks reflective pigment, called "roy orbison," with one that lacks black pigment, called "nacre." The offspring had only yellow pigment in their skin, essentially looking clear. White named the new breed "casper."
The fish's brain, heart, and digestive tract are also visible, allowing researchers to study genetic defects of these organs from early embryonic development through adulthood. White hopes this tool will provide insight into how mutated genes cause diseases ranging from Alzheimer's disease to inflammatory bowel disease.
"What happens in a living organism is different than what happens in a dish," White says.
Elizabeth Andrews | EurekAlert!
A Varied Menu
25.03.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau
Key evidence associating hydrophobicity with effective acid catalysis
25.03.2019 | Tokyo Metropolitan University
DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.
The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.
"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
25.03.2019 | Trade Fair News
25.03.2019 | Life Sciences
25.03.2019 | Information Technology