The National Institutes of Health know a good investment when they see one, and they definitely see one in Joe Lachance, researcher in the Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology. And to prove it, the NIH recently granted Lachance an R35 Maximizing Investigators’ Research Award (MIRA).
The grant, valued at $1.88 million over five years, will support Lachance’s research strategy, which includes the analysis of ancient and modern genomes, mathematical modeling, and the development of new bioinformatics tools.
Lachance, whose research bridges the gap between evolutionary genetics and genetic epidemiology, is motivated by several questions: How have hereditary disease risks evolved in the recent past? What sorts of genetic architectures are more likely to result in health inequities? How can genomic medicine be extended to people with different ancestries?
“We’ve taken an evolutionary perspective toward genetic medicine and global health,” says Lachance, assistant professor in the School of Biological Sciences, whose research is directly related to the NIH’s All of Us initiative.
The R35 MIRA program was designed to increase the stability of funding for NIGMS-supported investigators like Lachance, improving their ability to take on ambitious projects and take more creative approaches to biomedical problems.
“This grant, I think, demonstrates great confidence in our approach to the research,” Lachance said. “It enables us to devote more our time and energy on doing the actual science and developing the next generation of researchers.”
Corals create potions that fight bacterial attackers, but warming appears to tip the scales against the potions as they battle a bacterium common in coral bleaching, according to a new study. Reef conservation may offer hope: A particular potion, gathered from reefs protected against seaweed overgrowth, proved more robust.
The protected Pacific reefs were populated by diverse corals and shimmered with colorful fish, said researchers who snorkeled off of Fiji to collect samples for the study. Oceanic ecologists from the Georgia Institute of Technology compared coral potions from these reefs, where fishing was prohibited, with those from heavily fished reefs, where seaweed inundated corals because few fish were left to eat it.
The medicated solutions, or potions, may contain a multitude of chemicals, and the researchers did not analyze their makeup. This is a possible next step, but here the researchers simply wanted to establish if the potions offered any real defense against pathogens and how warming and overfishing might weaken it.
Conservation matters
“I thought I probably wouldn’t see antibiotic effects from these washes. I was surprised to see such strong effects, and I was surprised to see that reef protections made a difference,” said the study’s first author, Deanna Beatty.
“There is a lot of argument now about whether local management can help in the face of global stresses – whether what a Fijian village does matters when people in London and Los Angeles burn fossil fuels to drive to work,” said Mark Hay, the study’s principal investigator, Regents Professor and Harry and Linda Teasley Chair in Georgia Tech’s School of Biological Sciences.
“Our work indicates that local management provides a degree of insurance against global stresses, but there are likely higher temperatures that render the insurance ineffective.”
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Adding heat
The researchers collected three coral species along with seawater surrounding each species at protected reefs and at overfished reefs. In their Georgia Tech lab, they tested their solutions against the pathogen Vibrio coralliilyticus at 24 degrees Celsius (75.2 Fahrenheit), an everyday Fijian water temperature, and at 28 degrees (82.4 F), common during ocean heating events.
“We chose Vibrio because it commonly infects corals, and it’s associated with coral bleaching in these warming events. It’s related to other bleaching pathogens and could serve as a model for them as well,” Hay said.
“We chose 24 C and 28 C because they’re representative of the variations you see on Fijian reefs these days. Those are temperatures where the bacteria are more benign or more virulent,” Beatty said.
The data showed that warming disadvantaged all potions against Vibrio and conservation aided a potion from a key coral species. The team, which included coauthor Kim Ritchie from the University of South Carolina Beaufort, published its study in the journal Science Advances on Oct. 2. The research was funded by the National Institutes of Health’s Fogarty International Center, the National Science Foundation, and the Simons Foundation.
Deeper dive into the experiment
Seaweed hedges
The unprotected reefs’ shabby appearance portended their effects on the one potion associated with a key coral species.
“When you swim out of the no-fishing area and into the overfished area, you hit a hedge of seaweed. You have about 4 to 16% corals and 50 to 90% seaweed there. On the protected reef, you have less than 3% seaweed and about 60% corals,” Hay said.
Hay has researched marine ecology for over four decades and has seen this before, when coral reefs died off closer to home.
“Thirty years ago, when Caribbean reefs were vanishing, I saw overfishing as a big deal there, when seaweed took over,” he said, adding that global warming has become an overriding factor. “In the Pacific, many reefs that were not overfished have been wiped out in warming events. It just got too hot for too long.”
Distilling potion
The potions are products of the corals and associated microbes, which comprise a biological team called a holobiont.
To arrive at potions focused on chemical effects, the researchers agitated the coral holobionts and ocean water then freeze-dried and irradiated the resulting liquid to destroy remnants of life that could have augmented chemical action. Some viruses may have withstood sterilization, but it would have weakened any effect they may have had, if there were any.
Then the researchers tested the potions on Vibrio.
“All of the solutions’ defenses were compromised to varying extents at elevated temperatures where we see corals getting sick in the ocean,” Hay said.
But reef protection benefited the potion taken from the species Acropora millepora.
“The beneficial effect in the solution tested in the lab was better when Acropora came from protected areas, and this difference became more pronounced at 28 degrees Celsius,” said Beatty, who finished her Ph.D. with Hay and is now a postdoctoral researcher at the University of California, Davis.
Acropora architecture
Of the three species with potions that were tested, Acropora millepora may be a special one.
It is part of a genus – larger taxonomic category – containing about 150 of the roughly 600 species in Pacific reefs, and Acropora are core builders of reef structures. They grow higher as sea level rises, helping maintain healthy positions for whole reefs.
“Acropora are big and branching and make lots of crevices where fish live. The evolution of lots of reef fish parallels the evolution of Acropora in particular,” Hay said.
If fish can hang on, they may buy Acropora more time, and coral reefs perhaps, too.
Also READ: When Coral Species Vanish, Their Absence Can Imperil Surviving Corals
These researchers coauthored the study: Deanna Beatty, Jinu Valayil, Cody Clements, and Frank Stewart of Georgia Tech. The research was funded by the National Institutes of Health (grant 2 U19 TW007401-10), the National Science Foundation (grant OCE 717 0929119), the Simons Foundation (grant 346253), and the Teasley Endowment. Any findings, conclusions, or recommendations are those of the authors and not necessarily of the sponsors. DOI: https://doi.org/10.1126/sciadv.aay1048
Writer & Media Representative: Ben Brumfield (404-272-2780), email: ben.brumfield@comm.gatech.edu
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The College of Sciences held its annual summer dinner on Sept. 18, hosted by Susan Lozier, the new dean and Betsy Middleton and John Clark Sutherland Chair of the College of Sciences. The gathering has become a tradition for welcoming new members; recognizing excellence in research, instruction, and service; and affirming the College’s special community of scholars.
Tim Cope, Christine Heitsch, and Marvin Whiteley received the 2019 Faculty Mentor Awards. Cope and Whiteley are professors in the School of Biological Sciences; Heitsch is a professor in the School of Mathematics.
Nominations for these awards come from early-career faculty. Nominators cite mentors’ willingness to make introductions, review proposals, and develop professional training programs as extremely helpful as they get familiar with and navigate their environment and roles.
"[Y]our recognition also shines a bright light on your school and the College of Sciences, for which we are grateful.”
Also celebrated at the 2019 Summer Dinner were recipients of distinguished faculty awards, funded through the generosity of alumni and friends.
Greg Blekherman, Martin Mourigal, and Ronghu Wu received the Cullen-Peck Fellowship Awards. These are made possible by a gift from alumni couple Frank Cullen and Libby Peck. The goal is to encourage the development of especially promising mid-career faculty. Bleckherman is an associate professor of mathematics, Mourigal is an assistant professor of physics, and Wu is an associate professor of chemistry and biochemistry.
Kim Cobb, professor of Earth and atmospheric sciences, received the 2019 Gretzinger Moving Forward Award. This is made possible by a gift from alumnus Ralph Gretzinger and his late wife, Jewel. The award recognizes leadership of a school chair or senior faculty member who has played a pivotal role in diversifying the composition of faculty, creating a family-friendly environment, and providing a supportive environment for early-career faculty.
Jennifer Glass, associate professor of Earth and atmospheric sciences, received the 2019 Eric R. Immel Memorial Award for Excellence in Teaching. This award is supported by an endowment fund given by alumnus Charles Crawford to recognize exemplary instruction of foundational courses.
“I am pleased that your distinction in research, teaching, and mentoring brings recognition your way,” Lozier said. “But your recognition also shines a bright light on your school and the College of Sciences, for which we are grateful.”
Lozier also welcomed faculty who joined in the 2019-20 academic year, herself included as professor of Earth and atmospheric sciences. Also present were Meghan Babcock and Keaton Fletcher, School of Psychology; Marcus Cicerone and Joshua Kretchmer, School of Chemistry and Biochemistry; and Glen Evenbly, School of Physics. Unable to attend were Alex Blumenthal, School of Mathematics, and Alonzo Whyte, School of Biological Sciences.
“As you set out on your academic journey, please know that we are here to support, mentor, and advise you along the way,” Lozier said. “Your good fortune will be ours as well.”
The Office of International Initiatives announces the launch of the Georgia Tech Guide for Responsible International Activities, a new online resource regarding guidelines, policies, and procedures around the Institute’s global activities and partnerships.
This summer, the Office of International Initiatives convened a working group of members of the Office of the Executive Vice President for Research and the Office of the Provost to develop a resource to guide educational and research activities that happen abroad. The major deliverables of the working group were designed to help Georgia Tech make decisions and ensure proper planning, compliance, and transparency around all international activities.
“Georgia Tech is proud to engage with researchers, scholars, and institutions all over the world as an expression of the Institute’s motto of Progress and Service,” said Chaouki T. Abdallah, Georgia Tech’s executive vice president for Research. “We remain wholeheartedly committed to those important global collaborations, but we must safeguard the Institute, and ensure all activities are fully transparent and in compliance with Georgia Tech policies, as well as applicable government laws and regulations.”
Site users can find direct links to Georgia Tech resources, policies, and relevant campus contacts for offices and units that manage a variety of issues, including export control; managing conflicts of interest; appointments at other institutions; intellectual property; materials, data, and confidential information; the Foreign Corrupt Practices Act (FCPA); international agreements; disclosing foreign relationships; lab tours; hosting foreign visitors; and international travel.
“Georgia Tech promotes a culture of global engagement and believes that our community is enriched through opportunities to study, work, serve, or do research abroad,” said Rafael L. Bras, provost and executive vice president for Academic Affairs. “Thanks to the working group, the guide now provides access to Tech’s standing policies and procedures governing international activities in one centralized location.”
The guide will be maintained by the Office of International Initiatives and will be available on faculty and staff resource pages at several touchpoints, including global.gatech.edu, research.gatech.edu, and provost.gatech.edu, among others.
The working group also refined Georgia Tech’s Guiding Principles for International Activities, a standard set of objective criteria used by the Office of International Initiatives for measuring each international activity’s impact on academic activities, value to the Institute, compliance with applicable policies, sustainability and viability, and risk assessment and mitigation concerns.
Georgia Tech is also in the process of creating an International Advisory Committee comprised of representatives of the administration, faculty, and staff. The committee will be chaired by Yves Berthelot, vice provost for International Initiatives, and will provide guidance and advice regarding how Georgia Tech engages internationally (e.g. research, MOUs, master research agreements, etc.).
“Our success in international activities must be assessed in full consideration of geopolitical factors, as well as current and potential state and federal regulations and legislation,” said Berthelot. “With those considerations in mind, the work of the committee will prove vital for Georgia Tech as we continue to grow our relationships across the world and explore new opportunities to engage globally.”
Nominations for the committee are currently being accepted through Oct. 7. Faculty and staff are encouraged to submit self-nominations or nominations for a colleague. Details on the final committee roster will be made available via the online tool, once finalized. To self-nominate or nominate a colleague for the committee, or for more information on the working group’s activities, contact Monique Tavares, director of Global Operations at mtavares@gatech.edu.
Editor's Note: This essay by Kimberly Chen and Matthew Herron was originally published in The Science Breaker on Sept. 10, 2019. It is reposted here with permission.
Discussions about the evolution of multicellularity tend to focus on animals and plants, but there have actually been at least 25 independent origins of multicellularity in the history of life on this planet, including fungi, slime molds, several groups of algae, cyanobacteria and myxobacteria. So how did early single cells evolve into organisms consisting of multiple cells, and why? What were the advantages of being a multicellular organism?
It would be helpful in answering these critical questions if we could study the fossil history of multicellular organisms. However, few fossils have been found that show the earliest stages of the transition to multicellular life. Most such transitions happened hundreds of millions or even billions of years ago, and fossils that old are very rare. So it is really hard to know just what happened that far back.
Since we couldn't learn much from fossils, we used experimental evolution to replay life's tape in the laboratory. One favored driver for the evolution of multicellularity is Predation. Because most predators can only consume prey up to a certain size, getting bigger can provide protection against being eaten, and one way for single-celled organisms to get bigger is to form multicellular structures.
We used single-celled, free-swimming green algae (Chlamydomonas reinhardtii) to explore the possible evolution of multicellularity. The predators we used in our experiment are filter-feeding ciliates (Paramecium tetraurelia). Despite being unicellular, these ciliates are larger and graze on small algae by sweeping them into their mouths with hairlike structures called cilia. We cultured some algae with predators and some without predators for a year to see if predators would increase the evolution of multicellularity.
Single-celled algae normally multiply by a process called multiple fission, where a cell goes through one to three divisions to produce two, four or eight daughter cells. These daughters then hatch out of the mother cell wall to start the cycle again. By the end of our experiment, some of the cultures grown with predators had become multicellular by modifying their cell life cycle. In these evolved multicellular algae, we did not observe the last hatching step when the cell cycle is about to complete.
Instead, we found that each daughter cell continued its cell cycle within the mother cell wall, leading to multicellular clusters. Strictly speaking, cells in each cluster are descendants of a mother cell, and are genetic clones of each other. As clusters continue to grow bigger, they reach a limit and start to release single cells or small clusters of cells. In a separate experiment, we further showed that it is the cluster formation rather than other prey defenses that protects cells from predation. Selective pressure through predators, therefore, can favor the increase of clusters over single cells.
The multicellular life cycle is genetically fixed in the evolved multicellular algae, continuing even when they are grown in normal growth conditions without predators. But there is a price to pay. In nature, single-celled algae use slim threadlike structures called flagella to swim towards the light they need for photosynthesis. However, in the evolved multicellular algae each cell's flagella, even though they are present and active, are trapped within the mother cell wall. As a result, the multicellular clusters do not show noticeable movement. Such a drawback can be mitigated in the laboratory, since we culture these algae in an incubator with an ample supply of light. They might not be so lucky in nature.
From this experiment, we learned that multicellularity evolves readily in response to predation. This initial transition, although being a key step towards more complex life, does not seem to require organisms like green algae to evolve something new. Rather, this can be accomplished through a small modification to the existing cell cycle. The multicellular algae that evolved in our experiment also provide opportunities for further evolution experiments. For example, will they be able to regain the ability to swim? Can they evolve a division of labor, with cells becoming specialized to perform different tasks as we see in more complex multicellular organisms? These questions are under our current investigations.
Kimberly Chen is a postdoctoral researcher and Matthew Herron is a senior research scientist in the School of Biological Sciences.
Editors Note: This story is an abridged version of an article by Kelsey Abernathy and Selena Perrin published originally on Aug. 29, 2019, by the Scheller College of Business. A different headline was set for the College of Sciences audience.
How do you stop millions of pounds of heat-trapping CO2 from ever being emitted? In Georgia Tech’s Summer 2019 Carbon Reduction Challenge, student interns used their ingenuity to identify opportunities for scalable carbon reduction projects at a wide variety of partnering organizations. In doing so, they delivered large energy and cost savings to their employers.
Over the 10-week challenge, the students benefited from frequent coaching sessions led by faculty co-directors Kim Cobb, Director of the Global Change Program and professor in the School of Earth and Atmospheric Sciences, and Beril Toktay, Director of the Ray C. Anderson Center for Sustainable Business and professor in the Scheller College of Business.
Now in its third year, the internship-based Challenge has resulted in a total of over 30 million pounds of avoided CO2 emissions while delivering hundreds of thousands of dollars in avoided energy costs to partner organizations. In this year’s Challenge, 45 students from Georgia Tech, Agnes Scott College, Clemson University, Emory University, Georgia State University, and the University of Georgia competed for prizes provided by the Sheth Foundation.
On August 13, students presented their Summer 2019 projects to the general public and key industry leaders at the Challenge’s Summer Poster Expo at the Georgia Tech Scheller College of Business. Partnering organizations included Agnes Scott College, AT&T, Boeing, Emory University, Hartsfield-Jackson Atlanta International Airport, Jacobs Engineering, Michaud Cooley Erickson, and SunTrust Banks.
The top prize of $5,000 was awarded to Georgia Tech College of Sciences students Rebecca Guth-Metzler, Brooke Mancinelli-Rothschild, and Priyam Raut, who worked to implement a number of energy-saving initiatives in the Petit Institute for Bioengineering and Bioscience Building. Working with Georgia Tech Facilities, they replaced fluorescent light bulbs with LED bulbs and created a system for bundling energy-intensive autoclave loads. When fully implemented, their proposed changes will result in over 250,000 pounds of CO2 reductions per year.
“Our scientific research requires that we work in labs that are energy-intensive,” the team said. “We saw the Carbon Reduction Challenge as an opportunity to advocate for updates to our lab building and to lead the way toward more environmentally friendly lab practices.”
The second prize went to a team that developed a proactive plan to recycle aluminum in SunTrust signage that will need to be replaced as the company rebrands following its merger with BB&T. This project will save 1.2 million pounds of CO2 and generate a revenue of $125,000.
Two projects tied for third place. One is a project to upgrade dozens of outdoor lighting fixtures to LEDs at Michaud Cooley Erickson in Minneapolis, Minnesota, which will save 62,000 pounds of CO2 and $5,500 per year. The other project was a proposal for a more efficient lighting schedule for sprawling buildings at the Boeing campus in Seattle, Washington, which will translate to a savings of 6 million pounds of CO2 and $700,000 per year. Honorable mentions were awarded to projects with Agnes Scott College, Jacobs Engineering, and SunTrust Banks.
Student interns’ innovative work at the Poster Expo illustrated that employees do not need to have “sustainability” in their job title in order to be successful climate champions at work. “The Carbon Reduction Challenge is a particularly innovative real-world learning opportunity,” said Andrea Pinabell, President of Southface Institute, who served as a judge. “It equips students for success in an era of increasing interest in sustainable and climate-driven solutions.”
Top Three Teams
First Place ($5000)
Georgia Tech Labs Project
Rebecca Guth-Metzler (Biochemistry, second-year PhD student)
Brooke Mancinelli-Rothschiled (Biochemistry, second-year PhD student)
Priyam Raut (Bioinformatics, MS ’20)
Second Place ($3000)
SunTrust Banks Project
Nicholas Loprinzo (Industrial and Systems Engineering, BS ’20)
Raina Parikh (double major: Business Administration, International Affairs and Modern Languages; BS ’21)
Sarah Poersch (Business Administration, BS ’19)
Hongyangyang Shi (Analytics, MS ’19)
Athara Vaidya (Georgia State University, Analytics, MS ’19)
Third Place (tie, $1000 each)
Boeing Project
Kian Halim (Earth and Atmospheric Sciences, BS ’21)
Louis Hou (Business Administration, BS ’20)
Sam Shapiro (Computer Science, BS ’20)
Chris Wink (Business Administration, BS ’20)
Michaud Cooley Erickson Project
Nic Fite (Electrical Engineering, BS ’22)
If your ancestry in the United States stretches back more than 250 years, you may have Native American forbears. A new population genetics study shows that Americans with early European or early African ancestry can also have Native American gene groups.
Those Americans usually have family roots near the traditional homes of the respective tribes found in their genes, according to research led by the Georgia Institute of Technology. But where the descendants are today differs between these groups.
“People of Western European heritage have Native gene sequences from tribes that were located near where they now live,” said Andrew Conley, who led the study and is a research scientist in Georgia Tech’s School of Biological Sciences. “For African descendants, Native American ancestry looks like it came from regional groups of Native Americans in the southeastern United States.”
Many Americans descending from enslaved Africans later left the South in the Great Northward Migration, took those Native American sequences with them, and apparently no longer significantly reproduced with indigenous populations.
Americans with European heritage going back to Spain, mostly people who immigrated to the U.S. from Mexico, carry sequences from Native American ancestors who were traditionally located in what is Mexico today. This group also carries the most Native American genetic sequences by far, roughly 40% of their total genome, according to the study.
The researchers came to their conclusions by tracking haplotypes, patterns of genetic variants that are passed on by one parent, and that are typical for certain regions and peoples. They published their results in the journal PLoS Genetics on September 23, 2019.
“Haplotype combinations are very different between European, African and Native American ancestries and specific to locations,” Conley said.
The data was extracted from a much larger study, The Health and Retirement Study, sponsored by the National Institute on Aging (NIA) and conducted by the University of Michigan. That study also followed health and finance over time but included genomes and geography. Neither the NIA nor Michigan was part of the Georgia Tech study.
Americans of early African heritage have about 1.0% and of Western European heritage about 0.1% Native American haplotypes, though the difference in those numbers can be deceiving. The native ancestry probably lies a similar number of generations back for both groups.
“With African Americans, it correlates to about eight to nine generations back and probably ends there,” Conley said. “With Western European ancestors, we think about eight to 10 generations ago, and the contact with Native Americans could have also been more continuous.”
Further immigration from Europe likely dropped the percentage of Native American ancestry for the overall sample of Americans with Western European heritage.
“Particularly in the Mid-Atlantic and the Northeast there is almost no Native American ancestry among European descendants,” Conley said. “When you go out West, that’s where you have the most Native American ancestry in European populations.”
There was also an outlier group with European heritage from Spain.
“In parts of the Southwest, there are people of Spanish descent with also distinctive Native American ancestry. These groups call themselves Hispanos or Nuevomexicanos,” Conley said. “Their native American ancestry does not come from present-day Mexico. There were Spanish settlers in the region 400 years ago, and they could be the European ancestors of the Nuevomexicanos.”
The following coauthors from Georgia Tech collaborated on the study: King Jordan and Lavanya Rishishwar. Any findings, conclusions, or recommendations are those of the study’s authors.
Writer & Media Representative: Ben Brumfield (404-660-1408), email: ben.brumfield@comm.gatech.edu
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Spasticity is a condition in which muscles are contract strongly, resulting stiffness or tightness, and quite often, pain. Usually caused by damage to the brain or spinal cord, it’s particularly common in people with neurological maladies like cerebral palsy or stroke.
Cerebral palsy (CP) is the most common cause of physical disability in children in most developed countries, and spastic CP is the most common form of the disorder. For these patients (and others), spasticity can be severely debilitating, negatively impacting their movement, speech, gait, and overall quality of life.
The lab of Lena Ting, professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and in the Division of Physical Therapy in Emory’s Department of Rehabilitation Medicine, is tackling the problem, shedding new light on issues underlying spasticity.
Ting’s lab is part of an international collaborative effort with a recently published research article in the open access scientific journal, PLOS One. She is corresponding author of, “Interaction between muscle tone, short-range stiffness and increased sensory feedback
gains explains key kinematic features of the pendulum test in spastic cerebral palsy: A
simulation study.”
The pendulum test is a sensitive clinical assessment of spasticity in which the lower leg is
dropped from the horizontal position and the features of leg motion are recorded. “This problem actually arose out of a homework problem for my Computational Neuromechanics class, where we simulate the leg as a pendulum,” said Ting.
In typically-developed people, the swinging leg behaves like a damped pendulum, with the angle of leg swing decreasing as it oscillates several times before coming to rest. In children with spastic CP, three key differences in the leg motion are observed: Reduced angle of leg swing in the first oscillation, fewer oscillations, and the coming to rest at a less vertical angle.
Overall, the decrease in the first swing has been found to be the best predictor of spasticity severity, but why this is the case is has not been clear. Ting’s team hypothesized that increased muscle tone– the continual contraction of muscles while at rest–accounts for both the reduced leg swing and the non-vertical resting leg angle. This idea contrasts with the clinical explanation of spasticity as an abnormal increase in the activation of reflexes as the leg is stretched with higher velocities.
“We were stumped because the clinical explanation of increased velocity-dependent reflexes didn’t generate realistic motion,” Ting said. “But we happened to be working on a different research project studying an interesting property of muscles called short-range stiffness, which increases when muscles are activated. We wanted to know if this very rapid rise and drop of resistive force in muscles when they are stretched could explain the parts of the pendulum test that were giving us a hard time in the simulation.”
So the researchers developed and tested a physiologically-plausible computer simulation of how muscle tone and reflexes would interact to reproduce key features of the pendulum test for spasticity across a range of severity levels. Their new model helps to explain a whole range of pendulum test kinematics in people with and without CP.
“Increased muscle tone plays a primary role in generating a key feature of the leg motion that is most closely related to the level of spasticity,” Ting explained. “Even when reflexes are increased, can only account for pendulum test results across the spectrum of spasticity severity if we also increase muscle tone and short-range stiffness. This is exciting because the pendulum test is more objective than a clinician’s subjective assessment of leg stiffness. And with our model we can now begin to understand how multiple mechanisms of spasticity might interact to cause abnormal body motion, not just in the pendulum test, but in everyday movements.”
Lead author of the paper was Friedl De Groote, assistant professor in the Department of Movement Sciences at KU Leuven in Belgium. Other authors were both researchers from Ting’s lab, Kyle Blum and Brian Horslen.
Microbes live inside crowded communities in the environment and in hosts. Many wield a toxin-tipped harpoon called the Type 6 Secretion System (T6SS) to poke and kill competitors. The pathogenic bacterium Vibrio cholerae uses its T6SS weapon to survive in water and cause massive outbreaks of fatal cholera. In places like Yemen and Haiti, where water supplies are often contaminated and proper sanitation techniques are unavailable, cholera epidemics cause thousands of deaths. Only a few V. cholerae T6SS toxins have been described in prior studies that focused on outbreak strains, but the Hammer lab suspected novel toxins might be discovered by examining less-studied samples from environmental sources. In a collaborative study published in Genome Biology with Georgia Tech colleagues from the Jordan and Yunker labs, graduate students Cristian Crisan and Aroon Chande develop a computational tool, find several new T6SS toxins, and show that one of them is highly efficient at killing competitors. Currently, Cristian is studying the molecular mechanism by which another of the toxins can kill other cells.
True or false? Bacteria living in the same space, like the mouth, have evolved collaborations so generous that they are not possible with outside bacteria. That was long held to be true, but in a new, large-scale study of microbial interactions, the resounding answer was “false.”
Research led by the Georgia Institute of Technology found that common mouth bacteria responsible for acute periodontitis fared better overall when paired with bacteria and other microbes that live anywhere but the mouth, including some commonly found in the colon or in dirt. Bacteria from the oral microbiome, by contrast, generally shared food and assistance more stingily with gum infector Aggregatibacter actinomycetemcomitans, or Aa for short.
Like many bacteria known for infections they can cause – like Strep – Aa often live peacefully in the mouth, and certain circumstances turn them into infectors. The researchers and their sponsors at the National Institutes of Health would like to know more about how Aa interacts with other microbes to gain insights that may eventually help fight acute periodontitis and other ailments.
“Periodontitis is the most prevalent human infection on the planet after cavities,” said Marvin Whiteley, a professor in Georgia Tech’s School of Biological Sciences and the study’s principal investigator. “Those bugs get into your bloodstream every day, and there has been a long, noted correlation between poor oral hygiene and prevalence of heart disease.”
Unnatural pairing
The findings are surprising because bacteria in a microbiome have indeed evolved intricate interactions making it seem logical that those interactions would stand out as uniquely generous. Some mouth microbes even have special docking sites to bind to their partners, and much previous research has tightly focused on their cooperations. The new study went broad.
“We asked a bigger question: How do microbes interact with bugs they co-evolved with as opposed to how they would interact with microbes they had hardly ever seen. We thought they would not interact well with the other bugs, but it was the opposite,” Whiteley said.
The study’s scale was massive. Researchers manipulated and tracked nearly all of Aa’s roughly 2,100 genes using an emergent gene tagging technology while pairing Aa with 25 other microbes — about half from the mouth and half from other body areas or the environment.
They did not examine the mouth microbiome as a whole because multi-microbial synergies would have made interactions incalculable. Instead, the researchers paired Aa with one other bug at a time — Aa plus mouth bacterium X, Aa plus colon bacterium Y, Aa plus dirt fungus Z, and so on.
“We wanted to see specifically which genes Aa needed to survive in each partnership and which ones it could do without because it was getting help from the partner,” said Gina Lewin, a postdoctoral researcher in Whiteley’s lab and the study’s first author. They published their results in the Proceedings of the National Academy of Sciences.
Q & A
How could they tell that Aa was doing well or poorly with another microbe?
The researchers looked at each of Aa’s genes necessary for survival while it infected a mouse -- when Aa was the sole infector, when it partnered with a fellow mouth bacterium and when paired with a microbe from colon, dirt, or skin.
“When Aa was by itself, it needed a certain set of genes to survive – like for breathing oxygen,” Lewin said. “It was striking that when Aa was with this or that microbe that it normally didn’t live around, it no longer needed a lot of its own genes. The other microbe was giving Aa things that it needed, so it didn’t have to make them itself.”
“Interactions between usual neighbors — other mouth bacteria — looked more frugal,” Whiteley said. “Aa needed a lot more of its own genes to survive around them, sometimes more than when it was by itself.”
[Ready for graduate school? Here's how to apply to Georgia Tech.]
How did the emerging genetic marking method work?
To understand “transposon sequencing,” picture a transposon as a DNA brick that cracks a gene, breaking its function. The brick also sticks to the gene and can be detected by DNA sequencing, thus tagging that malfunction.
Every Aa bacterium in a pile of 10,000 had a brick in a random gene. If Aa’s partner bacterium, say, E. coli, picked up the slack for a broken function, Aa survived and multiplied even with the damaged gene, and researchers detected a higher number of bacteria containing the gene.
Aa surviving with more broken genes meant a partner microbe was giving it more assistance. Aa bacteria with broken genes that a partner could not compensate for were more likely to die, reducing their count.
Does this mean the mouth microbiome does not have unique relationships?
It very likely does have them, but the study’s results point to not all relationships being cooperative. Some microbiomes could have high fences and share sparsely.
“One friend or enemy may be driving your behavior, and other microbes may just be standing around,” Lewin said.
Smoking, poor hygiene, or diabetes — all associated with gum disease — might be damaging defensive microbiomes and allowing outside bacteria to help Aa attack gum tissue. It’s too early to know that, but Whiteley’s lab wants to dig deeper, and the research could have implications for other microbiomes.
Also read: Test for Life-Threatening Nutrient Deficit Made From Bacteria Entrails
These researchers coauthored the study: Apollo Stacy from the National Institute of Infectious Diseases and the National Institute of General Medical Sciences, Kelly Michie from Georgia Tech, and Richard Lamont from the University of Louisville. The research was funded by the National Institutes of Health’s National Institute of Infectious Diseases (grants R01DE020100, R01DE023193) and the National Institutes of Health (grants F32DE027281, F31DE024931). Any findings, conclusions or recommendations are those of the authors and not necessarily those of the National Institutes of Health. Whiteley is also a Georgia Research Alliance Eminent Scholar and Co-Director of Emory-Children’s Cystic Fibrosis Center.
Writer & Media Representative: Ben Brumfield (404-660-1408), email: ben.brumfield@comm.gatech.edu
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