Ancient 'chewing gum' yields insights into people and bacteria of the past

Ancient 'chewing gum' yields insights into people and bacteria of the past

Researchers from the University of Copenhagen have succeeded in extracting a complete human genome from a thousands-of-years old "chewing gum." According to the researchers, it is a new untapped source of ancient DNA.

During excavations on Lolland, archaeologists have found a 5,700-year-old type of "chewing gum" made from birch pitch. In a new study, researchers from the University of Copenhagen succeeded in extracting a complete ancient human genome from the pitch.

It is the first time that an entire ancient human genome has been extracted from anything other than human bones. The new research results have been published in the scientific journal Nature Communications.

'It is amazing to have gotten a complete ancient human genome from anything other than bone,'' says Associate Professor Hannes Schroeder from the Globe Institute, University of Copenhagen, who led the research.

'What is more, we also retrieved DNA from oral microbes and several important human pathogens, which makes this a very valuable source of ancient DNA, especially for time periods where we have no human remains,' Hannes Schroeder adds.

Based on the ancient human genome, the researchers could tell that the birch pitch was chewed by a female. She was genetically more closely related to hunter-gatherers from the mainland Europe than to those who lived in central Scandinavia at the time. They also found that she probably had dark skin, dark hair and blue eyes.

Sealed in mud

The birch pitch was found during archaeological excavations at Syltholm, east of Rødbyhavn in southern Denmark. The excavations are being carried out by the Museum Lolland-Falster in connection with the construction of the Fehmarn tunnel.

'Syltholm is completely unique. Almost everything is sealed in mud, which means that the preservation of organic remains is absolutely phenomenal,' says Theis Jensen, Postdoc at the Globe Institute, who worked on the study for his PhD and also participated in the excavations at Syltholm.

'It is the biggest Stone Age site in Denmark and the archaeological finds suggest that the people who occupied the site were heavily exploiting wild resources well into the Neolithic, which is the period when farming and domesticated animals were first introduced into southern Scandinavia,' Theis Jensen adds.

This is reflected in the DNA results, as the researchers also identified traces of plant and animal DNA in the pitch -- specifically hazelnuts and duck -- which may have been part of the individual's diet.

Bacterial evolution

In addition, the researchers succeeded in extracting DNA from several oral microbiota from the pitch, including many commensal species and opportunistic pathogens.

'The preservation is incredibly good, and we managed to extract many different bacterial species that are characteristic of an oral microbiome. Our ancestors lived in a different environment and had a different lifestyle and diet, and it is therefore interesting to find out how this is reflected in their microbiome,' says Hannes Schroeder.

The researchers also found DNA that could be assigned to Epstein-Barr Virus, which is known to cause infectious mononucleosis or glandular fever. According to Hannes Schroeder, ancient "chewing gums" bear great potential in researching the composition of our ancestral microbiome and the evolution of important human pathogens.

'It can help us understand how pathogens have evolved and spread over time, and what makes them particularly virulent in a given environment. At the same time, it may help predict how a pathogen will behave in the future, and how it might be contained or eradicated,' says Hannes Schroeder.

Chewing gum, all-purpose glue or medicine?

• Birch pitch is a black-brown substance that is produced by heating birch bark. It was commonly used in prehistory for hafting stone tools as an all-purpose glue. The earliest known use of birch pitch dates back to the Palaeolithic.
• Pieces of birch pitch are often found with tooth imprints suggesting that they were chewed. As the pitch solidifies on cooling, it has been suggested that it was chewed to make it malleable again before using it for hafting etc.
• Other uses for birch pitch have also been suggested. For example, one theory suggests that birch pitch could have been used to relieve toothache or other ailments as it is mildly antiseptic. Other theories suggest, people may have used it as a kind of prehistoric tooth brush, to suppress hunger, or just for fun as a chewing gum.

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Materials provided by University of Copenhagen The Faculty of Health and Medical Sciences. Note: Content may be edited for style and length.

New therapy targets gut bacteria to prevent and reverse food allergies

New therapy targets gut bacteria to prevent and reverse food allergies

A new study identifies the species of bacteria in the human infant gut that protect against food allergies, finding changes associated with the development of food allergies and an altered immune response.

Every three minutes, a food-related allergic reaction sends someone to the emergency room in the U.S. Currently, the only way to prevent a reaction is for people with food allergies to completely avoid the food to which they are allergic. Researchers are actively seeking new treatments to prevent or reverse food allergies in patients. Recent insights about the microbiome -- the complex ecosystem of microorganisms that live in the gut and other body sites -- have suggested that an altered gut microbiome may play a pivotal role in the development of food allergies. A new study, led by investigators from Brigham and Women's Hospital and Boston Children's Hospital, identifies the species of bacteria in the human infant gut that protect against food allergies, finding changes associated with the development of food allergies and an altered immune response. In preclinical studies in a mouse model of food allergy, the team found that giving an enriched oral formulation of five or six species of bacteria found in the human gut protected against food allergies and reversed established disease by reinforcing tolerance of food allergens. The team's results are published in Nature Medicine.

"This represents a sea change in our approach to therapeutics for food allergies," said co-senior author Lynn Bry, MD, PhD, director of the Massachusetts Host-Microbiome Center at the Brigham. "We've identified the microbes that are associated with protection and ones that are associated with food allergies in patients. If we administer defined consortia representing the protective microbes as a therapeutic, not only can we prevent food allergies from happening, but we can reverse existing food allergies in preclinical models. With these microbes, we are resetting the immune system."

The research team conducted studies in both humans and preclinical models to understand the key bacterial species involved in food allergies. The team repeatedly collected fecal samples every four to six months from 56 infants who developed food allergies, finding many differences when comparing their microbiota to 98 infants who did not develop food allergies. Fecal microbiota samples from infants with or without food allergies were transplanted into mice who were sensitized to eggs. Mice who received microbiota from healthy controls were more protected against egg allergy than those who received microbiota from the infants with food allergies.

Using computational approaches, researchers analyzed differences in the microbes of children with food allergies compared to those without in order to identify microbes associated with protection or food allergies in patients. The team tested to see if orally administering protective microbes to mice could prevent the development of food allergies. They developed two consortia of bacteria that were protective. Two separate consortia of five or six species of bacteria derived from the human gut that belong to species within the Clostridiales or the Bacteroidetes could suppress food allergies in the mouse model, fully protecting the mice and keeping them resistant to egg allergy. Giving other species of bacteria did not provide protection.

"It's very complicated to look at all of the microbes in the gut and make sense of what they may be doing in food allergy, but by using computational approaches, we were able to narrow in on a specific group of microbes that are associated with a protective effect," said co-first author Georg Gerber, MD, PhD, MPH, co-director of the Massachusetts Host-Microbiome Center and chief of the Division of Computational Pathology in the Department of Pathology at the Brigham. "Being able to drill down from hundreds of microbial species to just five or six or so has implications for therapeutics and, from a basic science perspective, means that we can start to figure out how these specific bacteria are conferring protection."

To understand how the bacteria species might be influencing food allergy susceptibility, the team also looked at immunological changes, both in the human infants and in mice. They found that the Clostridiales and Bacteroidetes consortia targeted two important immunological pathways and stimulated specific regulatory T cells, a class of cells that modulate the immune system, changing their profile to promote tolerant responses instead of allergic responses. These effects were found both in the pre-clinical models and also found to occur in human infants.

The new approach represents a marked contrast to oral immunotherapy, a strategy that aims to increase the threshold for triggering an allergic reaction by giving an individual small but increasing amounts of a food allergen. Unlike this approach, the bacteriotherapy changes the immune system's wiring in an allergen-independent fashion, with potential to broadly treat food allergies rather than desensitizing an individual to a specific allergen.

"When you can get down to a mechanistic understanding of what microbes, microbial products, and targets on the patient side are involved, not only are you doing great science, but it also opens up the opportunity for finding a better therapeutic and a better diagnostic approach to disease. With food allergies, this has given us a credible therapeutic that we can now take forward for patient care," said Bry.

Bry and Gerber, along with senior author Talal Chatila, MD, of Boston Children's Hospital, are founders and have equity in ConsortiaTX, a company that is developing a live human biotherapeutic product (CTX-944). (Co-senior author Rima Rachid, MD, of Boston Children's Hospital, also has equity in the company.) ConsortiaTX is preparing for a Phase 1b trial in pediatric food allergy, followed by expansion into additional allergic diseases. ConsortiaTX has obtained an exclusive global license to the intellectual property related to the microbial discoveries published in the Nature Medicine paper.

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Materials provided by Brigham and Women's Hospital. Note: Content may be edited for style and length.

Bacteria made to mimic cells, form communities

Bacteria made to mimic cells, form communities

Rice University scientists have found a way to engineer a new kind of cell differentiation in bacteria, inspired by a naturally occurring process in stem cells.

They have created a genetic circuit able to produce genetically distinguished cells of Escherichia coli as the bacterium divides. By controlling this process, it is possible to create diverse communities of microbes that exhibit complex, non-native behaviors.

Rice synthetic biologist Matthew Bennett and Sara Molinari, a former student in the university's Systems, Synthetic and Physical Biology Ph.D. program, led the project to show how manipulating the genetic code of plasmids -- free-floating pieces of circular DNA in cells -- can be used to obtain stem cell-like differentiation in bacteria.

"Stem cells have the remarkable ability to divide asymmetrically," Bennett said. "Upon division, the original stem cell stays the same, but the new daughter cell has a completely new phenotype. That's asymmetric cell division, and multicellular organisms use it to help control their cellular makeup.

"As a synthetic biologist, I think a lot about creating and controlling differentiated cell types within a multicellular population," he said. "Here, we've taken what we know about stem cells and engineered the means to do it in bacteria."

The researchers reported the development, which they call asymmetric plasmid partitioning (APP), in Nature Chemical Biology.

Molinari first discovered how to force plasmids in E. coli to aggregate in a single cluster so they do not distribute homogeneously during cell division, but rather are inherited by only one of the two daughter cells. The plasmid-laden daughter cell remains identical to the progenitor cell, while its sibling becomes genetically distinct as it loses the genetic information present on the plasmids.

She then expanded the synthetic circuit to induce the simultaneous asymmetric partitioning of two plasmid species in a single cell, resulting in four genetically distinct E. coli. Some of the cells have motility programmed in; they can literally go their own way and help form patterns in the resulting colony.

"When we started, we were thinking about creating materials that have to be able to sense and adapt to an environment," said Molinari, who recently earned her doctorate at Rice. "We thought if we could mimic this feature of higher-order tissues, we would increase the robustness of our colonies and their ability to perform tasks. The challenge was to engineer a population of bacteria that becomes something else whenever it's needed."

Molinari and her colleagues hit the jackpot on their first try with E. coli. "There was no canonical way to engineer asymmetrical cell division," she said. "It was a crazy idea, and it magically worked the first time.

"But there was something we couldn't completely figure out about the system," Molinari said. "It took two years to find out I made a cloning mistake when I got this protein and put it in my plasmid. I had randomly added 17 amino acids at the beginning of the protein, and that made the whole system work."

With that knowledge, she proceeded to improve upon the hydrophobic proteins that cluster in cells while they bind to target plasmids, holding them in place.

Bennett noted natural processes either load enough plasmids into a cell to ensure some land in each daughter cell or actively pull plasmids into each of the new cells to ensure they remain identical. "We have shown we can outcompete those processes," he said.

APP could turn simple organisms into complicated systems that enhance understanding of multicellular life. "We're pretty good at designing bacteria," Bennett said. "We've been doing that for years now. I think the field has evolved to the point where we can do amazing things with bacteria and people are asking what else we can do."

The new discovery, he said, provides a path forward.

"There are three main hallmarks to multicellular life," he said. "One is differentiation through asymmetric cell division. Another is intercellular communication, which synthetic biologists have been engineering for years. And the third is cell adhesion, so cells stay where they're supposed to and stick to each other. If we can control all those things together, we can talk about engineering interesting multicellular lifeforms.

"It starts to feel a bit like science fiction, for sure," he said.

---

Story Source:

Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.

Bacteria made to mimic cells, form communities

Bacteria made to mimic cells

Rice University scientists have found a way to engineer a new kind of cell differentiation in bacteria, inspired by a naturally occurring process in stem cells.

They have created a genetic circuit able to produce genetically distinguished cells of Escherichia coli as the bacterium divides. By controlling this process, it is possible to create diverse communities of microbes that exhibit complex, non-native behaviors.

Rice synthetic biologist Matthew Bennett and Sara Molinari, a former student in the university's Systems, Synthetic and Physical Biology Ph.D. program, led the project to show how manipulating the genetic code of plasmids -- free-floating pieces of circular DNA in cells -- can be used to obtain stem cell-like differentiation in bacteria.

"Stem cells have the remarkable ability to divide asymmetrically," Bennett said. "Upon division, the original stem cell stays the same, but the new daughter cell has a completely new phenotype. That's asymmetric cell division, and multicellular organisms use it to help control their cellular makeup.

"As a synthetic biologist, I think a lot about creating and controlling differentiated cell types within a multicellular population," he said. "Here, we've taken what we know about stem cells and engineered the means to do it in bacteria."

The researchers reported the development, which they call asymmetric plasmid partitioning (APP), in Nature Chemical Biology.

Molinari first discovered how to force plasmids in E. coli to aggregate in a single cluster so they do not distribute homogeneously during cell division, but rather are inherited by only one of the two daughter cells. The plasmid-laden daughter cell remains identical to the progenitor cell, while its sibling becomes genetically distinct as it loses the genetic information present on the plasmids.

She then expanded the synthetic circuit to induce the simultaneous asymmetric partitioning of two plasmid species in a single cell, resulting in four genetically distinct E. coli. Some of the cells have motility programmed in; they can literally go their own way and help form patterns in the resulting colony.

"When we started, we were thinking about creating materials that have to be able to sense and adapt to an environment," said Molinari, who recently earned her doctorate at Rice. "We thought if we could mimic this feature of higher-order tissues, we would increase the robustness of our colonies and their ability to perform tasks. The challenge was to engineer a population of bacteria that becomes something else whenever it's needed."

Molinari and her colleagues hit the jackpot on their first try with E. coli. "There was no canonical way to engineer asymmetrical cell division," she said. "It was a crazy idea, and it magically worked the first time.

"But there was something we couldn't completely figure out about the system," Molinari said. "It took two years to find out I made a cloning mistake when I got this protein and put it in my plasmid. I had randomly added 17 amino acids at the beginning of the protein, and that made the whole system work."

With that knowledge, she proceeded to improve upon the hydrophobic proteins that cluster in cells while they bind to target plasmids, holding them in place.

Bennett noted natural processes either load enough plasmids into a cell to ensure some land in each daughter cell or actively pull plasmids into each of the new cells to ensure they remain identical. "We have shown we can outcompete those processes," he said.

APP could turn simple organisms into complicated systems that enhance understanding of multicellular life. "We're pretty good at designing bacteria," Bennett said. "We've been doing that for years now. I think the field has evolved to the point where we can do amazing things with bacteria and people are asking what else we can do."

The new discovery, he said, provides a path forward.

"There are three main hallmarks to multicellular life," he said. "One is differentiation through asymmetric cell division. Another is intercellular communication, which synthetic biologists have been engineering for years. And the third is cell adhesion, so cells stay where they're supposed to and stick to each other. If we can control all those things together, we can talk about engineering interesting multicellular lifeforms.

"It starts to feel a bit like science fiction, for sure," he said.

---

Story Source:

Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.

Bacteria made to mimic cells, form communities

Bacteria

Rice University scientists have found a way to engineer a new kind of cell differentiation in bacteria, inspired by a naturally occurring process in stem cells.

They have created a genetic circuit able to produce genetically distinguished cells of Escherichia coli as the bacterium divides. By controlling this process, it is possible to create diverse communities of microbes that exhibit complex, non-native behaviors.

Rice synthetic biologist Matthew Bennett and Sara Molinari, a former student in the university's Systems, Synthetic and Physical Biology Ph.D. program, led the project to show how manipulating the genetic code of plasmids -- free-floating pieces of circular DNA in cells -- can be used to obtain stem cell-like differentiation in bacteria.

"Stem cells have the remarkable ability to divide asymmetrically," Bennett said. "Upon division, the original stem cell stays the same, but the new daughter cell has a completely new phenotype. That's asymmetric cell division, and multicellular organisms use it to help control their cellular makeup.

"As a synthetic biologist, I think a lot about creating and controlling differentiated cell types within a multicellular population," he said. "Here, we've taken what we know about stem cells and engineered the means to do it in bacteria."

The researchers reported the development, which they call asymmetric plasmid partitioning (APP), in Nature Chemical Biology.

Molinari first discovered how to force plasmids in E. coli to aggregate in a single cluster so they do not distribute homogeneously during cell division, but rather are inherited by only one of the two daughter cells. The plasmid-laden daughter cell remains identical to the progenitor cell, while its sibling becomes genetically distinct as it loses the genetic information present on the plasmids.

She then expanded the synthetic circuit to induce the simultaneous asymmetric partitioning of two plasmid species in a single cell, resulting in four genetically distinct E. coli. Some of the cells have motility programmed in; they can literally go their own way and help form patterns in the resulting colony.

"When we started, we were thinking about creating materials that have to be able to sense and adapt to an environment," said Molinari, who recently earned her doctorate at Rice. "We thought if we could mimic this feature of higher-order tissues, we would increase the robustness of our colonies and their ability to perform tasks. The challenge was to engineer a population of bacteria that becomes something else whenever it's needed."

Molinari and her colleagues hit the jackpot on their first try with E. coli. "There was no canonical way to engineer asymmetrical cell division," she said. "It was a crazy idea, and it magically worked the first time.

"But there was something we couldn't completely figure out about the system," Molinari said. "It took two years to find out I made a cloning mistake when I got this protein and put it in my plasmid. I had randomly added 17 amino acids at the beginning of the protein, and that made the whole system work."

With that knowledge, she proceeded to improve upon the hydrophobic proteins that cluster in cells while they bind to target plasmids, holding them in place.

Bennett noted natural processes either load enough plasmids into a cell to ensure some land in each daughter cell or actively pull plasmids into each of the new cells to ensure they remain identical. "We have shown we can outcompete those processes," he said.

APP could turn simple organisms into complicated systems that enhance understanding of multicellular life. "We're pretty good at designing bacteria," Bennett said. "We've been doing that for years now. I think the field has evolved to the point where we can do amazing things with bacteria and people are asking what else we can do."

The new discovery, he said, provides a path forward.

"There are three main hallmarks to multicellular life," he said. "One is differentiation through asymmetric cell division. Another is intercellular communication, which synthetic biologists have been engineering for years. And the third is cell adhesion, so cells stay where they're supposed to and stick to each other. If we can control all those things together, we can talk about engineering interesting multicellular lifeforms.

"It starts to feel a bit like science fiction, for sure," he said.

---

Story Source:

Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.