Copper deficiency diseases can be devastating. Symptoms can range from crippling neurological degeneration in Menkes disease – a classic copper deficiency disease – to brittle bones, anaemia and defective skin pigmentation in gastric bypass patients. Unfortunately, very little is known about how the body uses this essential nutrient.
Knowing that melanocytes (the cells that give rise to hair, skin and eye pigmentation) are dramatically affected by the effects of copper deficiency, Elizabeth Patton from the University of Edinburgh, UK, and other colleagues from UK- and US-based labs decided to find out how melanocytes metabolise copper. Patton and her colleagues publish their results in Disease Models and Mechanisms on August 17, 2010 at http://dmm.biologists.org/.
Patton explains that zebrafish are a valuable research tool because they are an intermediate organism between mammals and the simpler creatures that scientists routinely use to study genetic disorders. She usually uses zebrafish to understand how melanocytes develop and how these cells can give rise to malignant melanoma, a lethal form of cancer. Testing compounds that she hoped might prevent malignant melanoma symptoms in zebrafish, she was puzzled to find a compound that caused the fish to lose their characteristic zebra-stripe patterns. After spending months trying to determine why the fish lost their stripes, she crossed paths with Jonathan Gitlin, a copper deficiency specialist from Vanderbilt University, USA, and realised that the stripeless fish might have copper deficiency.
To understand the molecular pathways involved in copper deficiency, Patton and Gitlin teamed up with Mike Tyers from the University of Edinburgh and developed an elegant method to probe copper metabolism in zebrafish. First, the team identified compounds that caused zebrafish to lose their stripes – indicating copper deficiency. Next, they identified the genes that each compound targeted by applying the compounds to yeast cells. Patton explains that most of the genes that control copper metabolism are very similar in yeast, zebrafish and humans, so the genes identified in this study should increase our understanding of what makes certain people susceptible to copper deficiency.
The team found that mutations in certain proteins that move nutrients around cells (trafficking components) increase the risk that carriers will be susceptible to copper deficiency when the copper supply is restricted, such as after gastric bypass surgery. Patton says, "You might have people with polymorphisms [variations in a single gene] in some of these trafficking components that are fine, but under certain environmental conditions some of the weaknesses are revealed."
This work demonstrates the utility of the coupled zebrafish-yeast approach for studying copper deficiency, but it can also be applied for studying other complex multifactorial diseases, particularly those with an environmental component. "There have been some beautiful studies looking at transport components in melanocytes, which have linked copper metabolism pathways with transport. What's new here is that we can investigate a gene-environment interaction," says Patton, who hopes to apply the method for studying cardiofaciocutaneous syndrome, a rare genetic disorder with crippling symptoms ranging from skin abnormalities to heart defects. In addition, her team plans to apply the method to investigate how drug candidates function in vivo.
REFERENCE: Ishizaki, H., Spitzer, M., Wildenhain, J., Anastasaki, C., Zeng, Z., Shaw, M., Erik Madsen, E., Gitlin, J., Marais, R., Tyers, M. Patton, E. E. (2010). Combined zebrafish-yeast chemical genetic screens reveal gene-copper nutrition interactions that modulate melanocyte pigmentation. Dis. Model. Mech. doi:10.1242/dmm.005769
Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin
Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology