The University of Texas at Austin scientists exploited the fact that all life on Earth shares common ancestry, and therefore shares sets of genes.
They found genes in yeast, for example, that humans use to make veins and arteries, even though yeasts have no blood vessels at all. Yeasts use those same genes to fix their cell walls in response to stress.
"Basically, we figured out a way to discover the genetic basis for disease by looking at organisms other than humans and finding disease equivalents," says Edward Marcotte, professor of chemistry and biochemistry.
To find the new genes, Marcotte and his graduate students developed a computer algorithm that first sifts through vast sets of existing genomic data for worms, mice, yeast, plants and humans. The algorithm pairs up sets of genes that overlap between these organisms and humans.
In doing so, it highlights genes that are known to work together to do one thing in the non-human organism, but the function of which are not yet known in humans. The scientists can then test those new genes in the lab to determine their function.
"The basic essence of the method is that there are ancient modules of genes that have been reused in different contexts over time," says Marcotte. "So the yeast uses a particular module with a particular set of inputs and outputs to do one task. Humans use this same module with different inputs and outputs to do another."
In the case of blood vessel formation, or angiogenesis, the scientists found 62 genes that yeast use to fix their cell walls that matched with a few genes known to be responsible for vein and artery formation in humans.
Developmental biologist John Wallingford and his graduate students then tested the human equivalents of the 62 yeast genes in developing frog embryos in the lab. This confirmed that eight of those 62 genes help build blood vessels in animals. Several of these genes were also confirmed in humans.
The newly found human angiogenesis genes are great candidates for drugs, says Marcotte.
"Tumors fool your body into feeding them by initiating blood vessel growth, and that's the reason we're interested in angiogenesis," says Marcotte. "So, genes for angiogenesis are common targets for chemotherapy. Some of the most effective chemotherapies block angiogenesis."
The scientists also found a set of genes in nematode worms involved in human breast cancer. Surprisingly, it is the same set of genes in the worms responsible for determining how many male offspring a parent worm births.
In plants, they found a gene that is involved with a genetic disorder called Waardenburg syndrome, which causes a significant fraction of cases of human deafness. (Strangely, plants use the gene as part of their system for sensing gravity, called gravitropism.)
The researchers are teasing out genes for a variety of human disorders, from mental retardation and birth defects to cataracts. Their goal is to find new genetic targets for therapy.
"By exploiting evolution and looking at lower organisms that don't even have the organs we're looking for—blood vessels or even heads—but share some of the underlying molecular processes, we're able to discover genes relevant to human diseases," says Marcotte.
Marcotte admits it may seem odd to look for human disease genes in something like a plant or yeast, but that the information is proving to be extremely useful, if not surprising.
"When we found the genes in plants responsible for Waardenberg syndrome in humans," he says, "we were screaming in the halls."
Marcotte, Wallingford and colleagues published their research in PNAS (Proceedings of the National Academy of Sciences).
Marcotte and Wallingford are members of the Center for Systems and Synthetic Biology and the Institute for Cellular and Molecular Biology. Wallingford, associate professor of molecular cell and developmental biology, is a Howard Hughes Medical Institute Early Career Scientist. Co-authors Kriston McGary, Tae Joo Park, John Woods and Hye Ji Cha are graduate students at The University of Texas at Austin.
For more information contact: Edward Marcotte, professor of chemistry and biochemistry, 512-471-5435; John Wallingford, associate professor of molecular cell and developmental biology, 512-232-2784.
Lee Clippard | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences