AP Biology class blog for discussing current research in Biology

Author: tracetylcholine

Planet of the (CRISPR-Edited, Cloned) Apes

Several months ago, scientists in China cloned five gene-edited macaque monkeys. The clones were made through the somatic cell nuclear transfer method (SCNT)—a process in which a viable embryo is created from a body cell and an egg cell—that was used to produce the first primate clones around a year ago. In this instance, however, the monkeys’ genomes were first edited using CRISPR-Cas9—a unique genome editing tool that enables geneticists to edit parts of the genome by removing, adding, or altering sections of the DNA sequence—to show symptoms of sleep disorders by eliminating BMAL1, one of the positive elements in the mammalian auto-regulatory TTFL, which is responsible for generating molecular circadian rhythms. The result? The monkeys exhibited a wide range of circadian disorder phenotypes, including elevated night-time locomotive activities, reduced sleep time, reduced circadian cycling of blood hormones, increased anxiety and depression, and other schizophrenia-like behaviors. 

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Macaque Monkey

Naturally, the results of the investigation triggered much backlash. According to Carolyn Neuhaus of The Hastings Center, the researchers viewed the suffering of the monkeys as a triumph, and failed to consider the moral implications of their investigation. “It’s very clear that these monkeys are seen as tools,” she told Gizmodo, the latter publication writing in a similar sentiment, “Their experiment is a minefield of ethical quandaries—and makes you wonder whether the potential benefits to science are enough to warrant all of the harm to these monkeys”. 

Nevertheless, the researchers involved in the experiment remain firm in their support of the experiment—the goal of which was to produce genetically identical monkey models of disease for biomedical research—on both moral and scientific grounds. “We believe that this approach of cloning gene-edited monkeys could be used to generate a variety of monkey models for gene-based diseases, including many brain diseases, as well as immune and metabolic disorders and cancer,” stated Qiang Sun, one of the research paper’s authors and director of the Nonhuman Primate Research Facility at the Chinese Academy of Science’s Institute of Neuroscience in Shanghai. Moreover, Reuters reported, “Xinhua [the state news agency] said the program, supervised by the institute’s ethics panel, was in line with international ethical standards for animal research”. Time will tell, ultimately, if the results of their experiment prove consequential on a larger scale. 

The Answer, My Friend, is … in Llama Poop?

New research recently published in the Journal of Archaeological Science reveals a key—albeit seemingly unlikely—indicator for the health of the Inca Empire: llama droppings. Led by paleoecologist Alex Chepstow-Lusty of the University of Sussex, a group of researchers has been able to accurately track the rise and fall of the Incan Empire by examining the oribatid mite population in Marcacocha, tiny spider relatives that once gorged on the feces of llamas passing through the region. Now a dried-up wetland in the mountains, Marcachoca was a small lake over 200 years ago, and a popular rest stop for Incan llama caravans on their way to and from the ancient city of Ollantaytambo. Thousands of llamas carrying trade goods like maize, salt, feathers, and coca leaves would descend upon Lake Marcacocha, where they would water themselves, drink, and defecate along the edges of the pool. Washed into the lake, their dung was then consumed by the resident, half-millimeter long mites. When the mites died, they sank into the lake mud, preserving their corpses  and allowing Alex Chepstow-Lusty to discover them in a sediment core centuries later. Of course, the more llamas that passed through Marcacocha, the more poop the mites had to eat and thus the larger their populations could grow. Conversely, a decline in the llama population would correspond to a decline in the mite population.

After counting the number of mites in each layer of the core, Chepstow-Lusty found that their population skyrocketed when the Incan Empire dominated the Andes from 1438 C.E. to 1533 C.E.—the “golden age” of the Incan Empire. Francisco Pizzaro’s conquest of the empire, however, initiated a massive die-off of Indigenous people and their animals alike, and, as a result, the number of mites took a nosedive. The mite population rose again once Old World animals such as cows, pigs, and horses were brought to the area, but ultimately began to decline again around 1720, when a smallpox epidemic decimated the region.

File:Machu Picchu 25.jpgLlama overlooking Machu Picchu, the most familiar icon of Inca civilization

Surprisingly, the researchers’ investigation of a second poop-eating microorganism, a genus of fungus called Sporormiella, contradicted the results offered by both the mite analysis and the historical record. Since Sporormiella live on herbivores and often reveal insights on the extinctions of large plant-eater populations, scientists often use Sporormiella spore counts to estimate the historical populations of big herbivores. However, the new study demonstrates that other factors can affect fungus populations in different environments, so relying solely on Sporormiella counts can give a misleading picture of population sizes. In the context of Marcacocha, Sporormiella counts responded to fluctuations in the lake’s water level, but didn’t correlate well with the chronology of the Inca Empire. “The spores may be saying more about the environmental conditions of the lake at that time,” according to Chepstow-Lusty, “rather than about the herbivores that may have been living around it.” Ultimately, moving forward, the researchers plan to conduct similar mite studies in Peru and other global locales to see if the technique holds its reliability. If proven reliable, the technique could be a powerful tool for uncovering the fate of other lost civilizations. 

We Didn’t Start the Fire…Gut Microbes Did.

Many scientists have hypothesized that infants’ gut microbiota could influence the development of their immune system. Recently, a test led by Drs. Christine C. Johnson at the Henry Ford Health System in Detroit and Susan Lynch at the University of California, San Francisco, but this theory to test. Specifically, they set out to examine the relationship between an infant’s gut microbiota and their relative risk of atopy and asthma. The researchers inspected the composition of gut microbes in stool samples from almost 300 infants—all part of a diverse study group born in and around Detroit between 2003 and 2007—by means of examining sequence variation within ribosomal RNA. Ultimately, the team found that the infants could be divided into 3 separate groups, each with distinct bacterial and fungal gut microbiota.

When blood samples obtained from the infants at 2 years of age were tested for sensitivity to allergens, the 3 microbiota groups had significantly different risks for allergen sensitivity. The “high-risk” microbiota group had a relatively lower abundance of certain bacteria and a higher level of some fungi, and was more likely to be diagnosed with asthma at 4 years of age. This seeming link between gut microbiota and allergy and asthma was also manifested when other factors associated with allergic disease—such as breastfeeding—were controlled. Moreover, the researchers found that the high-risk group had a distinct set of metabolites that lacked anti-inflammatory fatty acids and breast milk-derived oligosaccharides that were found in children in the low-risk microbiota group, increasing vulnerability to inflammation.

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Neonatal gut microbiota play a huge role in health and disease (Credit: Eric Atkins)

The researchers also mixed immune cells from healthy adult donors in solutions containing metabolites extracted from the infant’s stool samples. The high-risk group’s metabolite samples increased the amount of allergy-promoting immune cells interleukin-4, a cell-signaling protein associated with allergies, and also reduced T-regulatory cells, an essential group of immune cells that suppress allergic responses. This reduction in T-regulatory cells was also spurred by a lipid that the team identified, called 12,13-DiHOME, that was found at high levels in the high-risk group. Discussing this finding, Lynch expressed to The Scientist, “That for me is incredibly exciting as it suggests that microbial-associated metabolites in the neonatal gut may represent an important driver of early-life immune cell phenotypes associated with disease development in childhood.”

The team plans to conduct a similar study that will focus on environmental factors and how they may affect the development of the gut microbiota. According to Lynch, “Understanding the basis of human-microbial development may prove critical to unraveling the basis of allergy and asthma and to developing preventative therapeutic strategies.”

“Look! Up In The Sky! It’s a Bird! It’s a Plane! It’s…. A Blue-Throated Hillstar!

A decade ago, most scientists and bird-watchers believed that there were between 9,000 and 10,000 species of birds on the planet. A new study in 2016, however, led by the American Museum of Natural History, doubled that estimate, suggesting that there are 18,000 bird species in the world. One big step in the discovery of these unknown bird species was announced just several weeks ago, with the finding of a new species of hummingbird in Ecuador. Named Oreotrochilus cyanolaemus, or blue-throated hillstar, the species was discovered in the Andes by a multinational team of ornithologists from Ecuador, Venezuela, Denmark and Sweden. Dr. Francisco Sornoza-Molina of the Instituto Nacional de Biodiversida in Quito, Ecuador, and his colleagues first photographed the hillstar during fieldwork in the Ecuadorian highlands back in April of 2017; they would return later that spring to verify the finding.

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Hummingbird that resembles the blue-throated hillstar | Taken by Sheri L. Williamson

The blue-throated hillstar is approximately 13 centimeters in length and has a slightly curved beak, which it uses to reach the flowers of the chuquiragua, an Ecuadorian plant known as the “flower of the Andes” or “flower of true love” that is used to brew tea. It has a rich, deep-blue neck and greenish-blue head and body feathers.

Ecuador is rich in biodiversity, containing 132 hummingbird species out of the more than 300 in the world, but that doesn’t make the discovery any less surprising. Hummingbird expert and researcher at the University of New Mexico, Dr. Christopher Witt,  commented, “The hillstar hummingbirds occur in the most rugged, isolated, and inaccessible parts of the Andes, where they roost in caves, forage on the ground, and spend half their lives in hypothermic torpor, so the discovery of a new species in this group is incredibly exciting.” With estimates on the number of individuals of blue-throated hillstars varying between 250 and 750, ornithologists agree that the species is in danger of extinction, with its high-altitude habitat between the provinces of Loja and El Oro near the Pacific Ocean threatened by gold-mining, fire, and grazing. Commenting on the life-threatening conditions facing the blue-throated hillstar, Dr. Sornoza-Molina of the research team said, “Complete support from national and international conservation agencies is needed in order to save this species. The action plan for the conservation of this bird is creating a network of protected areas along its geographic range.”

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