Leading a new era in ancient DNA research

A new ancient DNA lab at Emory is mapping little-explored human lineages, studying genetics of the deep past to better understand modern-day populations of the Americas. Emory junior Rosseirys "Ro" De La Rosa is helping analyze DNA that she extracted from ancient bones unearthed in Uruguay — the remains of an Indigenous people known as the Charrúa. “Very few remains of the Charrúa have been found,” De La Rosa says. “They were largely wiped out by colonialism and a lot of mystery surrounds them. Anything that we can learn is important.” It may be possible to connect the ancient Charrúa to modern-day populations unaware of their link. “Culture matters,” says De La Rosa, who is continuing to work on the project remotely this semester. “Leaning about your own culture gives you a sense of unity and connection that you can pass down to others.” De La Rosa is a member of the Lindo Ancient DNA Laboratory, headed by John Lindo, Emory assistant professor of anthropology. The state-of-the-art facility, funded by major grants from National Geographic Explorer and the National Science Foundation, opened in January in Emory's Psychology and Interdisciplinary Sciences Building. It is one of the few in the world involved in every step of the complex process of solving mysteries surrounding ancient remains. "We build projects from the ground up," Lindo says. "We extract DNA from ancient remains here, sequence it here, analyze it here, and publish the results." Most previous ancient DNA work involves people of European ancestry. A focus of the Emory lab, however is exploring how environmental changes — including those caused by European contact — affected the biology of Indigenous and other populations of the Americas."Our work can connect people to ancestries they potentially don't know about," Lindo explains. "It can also give them insights into how historic, and even prehistoric, events may be affecting them today, especially in terms of health risks and disparities." eScienceCommons: Leading a new era in ancient DNA research

Read More........→July 26, 2023

The first high-res 3D images of DNA segments

Credit: Berkeley Lab

First-of-their-kind images by researchers at Berkeley Lab could aid in the use of DNA to build nanoscale devices.

An international team working at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has captured the first high-resolution 3-D images from individual double-helix DNA segments, attached at either end of gold nanoparticles. The images detail the flexible structure of the DNA segments, which appear as nanoscale "jump ropes". This unique imaging capability, pioneered by Berkeley Lab scientists, could aid in the use of DNA segments as building blocks for molecular devices that function as nanoscale drug-delivery systems, markers for biological research, and components for computer memory and electronic devices. It could also lead to images of disease-relevant proteins that have proven elusive for other imaging techniques, and of the assembly process that forms DNA from separate, individual strands. The shapes of the coiled DNA strands, which were sandwiched between polygon-shaped gold nanoparticles, were reconstructed in 3-D using a cutting-edge electron microscope
technique called individual-particle electron tomography (IPET).  This was combined with a protein-staining process and sophisticated software that provided structural details down to a scale of just 2 nanometres (nm), or about two billionths of a metre. "We had no idea about what the double-strand DNA would look like between the nanogold particles," said Gang Ren, a Berkeley Lab scientist who led the research. "This is the first time for directly visualising an individual double-strand DNA segment in 3-D." While the 3-D reconstructions show the basic nanoscale structure of the samples, Ren said the next step will be to improve the resolution to the sub-nanometre scale: "Even in this current state, we begin to see 3-D structures at 1- to 2-nanometre resolution," he said. "Through better instrumentation and improved computational algorithms, it would be promising to push the resolution to that visualising a single DNA

Berkeley Lab researchers Gang Ren (standing) and Lei Zhang. Photo by Roy Kaltschmidt/Berkeley Lab.

helix within an individual protein." The technique, he said, has already excited interest among some prominent pharmaceutical companies and nanotechnology researchers, and his science team already has dozens of related research projects being planned. In future studies, they could attempt to improve the imaging resolution for complex structures that incorporate more DNA segments as a sort of "DNA origami," Ren said. Researchers hope to build and better characterise nanoscale molecular devices using DNA segments that can, for example, store and deliver drugs to targeted areas in the body. "DNA is easy to program, synthesise and replicate, so it can be used as a special material to quickly self-assemble into nanostructures and to guide the operation of molecular-scale devices," he said. "Our current study is just a proof of concept for imaging these kinds of molecular devices' structures." His team's work is published in the journal Nature Communications. Source: futuretimeline.net

Read More........→April 18, 2016

Genes for longer and healthier life identified

From a 'haystack' of 40,000 genes in three different organisms, scientists have found genes that are involved in physical aging. If you influence only one of these genes, the healthy lifespan of laboratory animals is extended – and possibly that of humans, too.

Driven by the quest for eternal youth, humankind has spent centuries obsessed with the question of how exactly it is that we age. With advancements in molecular genetics in recent decades, the search for genes involved in the aging process has greatly accelerated. Until now, this was mostly limited to genes of individual model organisms such as the C. elegans nematode, which revealed that around 1% of its genes could influence life expectancy. However, researchers have long assumed that such genes arose during the course of evolution and in all living beings whose cells preserved a nucleus – from yeast to humans. Researchers at ETH Zurich and the JenAge consortium in Germany have now systematically gone through the genomes of three different organisms in search of the genes associated with the aging process that are present in all three species – and thus, derived from a common ancestor. Although they are found in different organisms, these so-called orthologous genes are closely related to each other, and they are all found in humans, too. To detect them, researchers examined around 40,000 genes in the nematode C. elegans, zebra fish and mice. By screening them, the scientists wanted to determine which genes are regulated in an identical manner in all three organisms in each comparable aging stage: young, mature and old. As a measure of gene activity, they recorded the amount of messenger RNA (mRNA) molecules found in the cells of these animals. mRNA is the transcript of a gene and the blueprint of a protein. When there are many copies of an mRNA of a specific gene, it is very active; the gene is said to be "upregulated". Fewer mRNA copies, to the contrary, are regarded as a sign of low activity. From this information, the researchers used statistical models to establish an intersection of genes that were regulated in the same manner in the worms, fish and mice. This showed that the three organisms have only 30 genes in common that significantly influence the aging process. 

From left to right: C. elegans nematode, zebra fish and mouse. Credit: Bob Goldstein [CC BY-SA 3.0]

By conducting experiments in which the mRNA of the corresponding genes were selectively blocked, the researchers pinpointed their effect on the aging process in nematode worms. With a dozen of these genes, blocking them extended the lifespan by at least five percent. One of these genes proved to be particularly influential: the bcat-1 gene. "When we blocked the effect of this gene, it significantly extended the mean lifespan of the nematode by up to 25 percent," says Professor Michael Ristow, coordinating author of the recently published study and Professor of Energy Metabolism at ETH. When the gene activity of bcat-1 was inhibited, branched-chain amino acids accumulated in the tissue, triggering a molecular signalling cascade that increased longevity. Moreover, the timespan during which the worms remained healthy was extended. As a measure of vitality, the researchers observed the accumulation of aging pigments, the speed at which the creatures moved, and how often the nematodes successfully reproduced. All of these parameters improved markedly. Professor Ristow has no doubt that the same mechanism occurs in humans: "We looked only for the genes that are conserved in evolution and therefore exist in all organisms including humans," he says. A follow-up study is already planned. "However, we can't measure the life expectancy of humans for obvious reasons," he adds. Instead, they plan to incorporate various health parameters, such as cholesterol or blood sugar levels in their study to obtain indicators on the health status of their subjects. Multiple branched-chain amino acids are already being used to treat liver damage and also feature in sports nutrition products. This follow-up study will deliver new and important indicators on how the aging process could be influenced and how age-related diseases might be prevented. "However, the point is not for people to grow even older – but rather, to stay healthy for longer," the researchers argue. Given the unfavourable demographics and steadily increasing life expectancy, it is important to extend the healthy life phase – or "healthspan" – and not to simply reach an even higher age that is characterised by chronic diseases. With such preventive measures, elderly people could greatly improve their quality of life, while at the same time cutting their healthcare costs by more than half. Source: http://www.futuretimeline.net

Read More........→January 17, 2016