"Very Fast CRISPR On Demand"
Taekjip Ha, Ph.D.
Bloomberg Distingushed Professor
Professor, Biophysics and Biophysical Chemistry
Professor, Biomedical Engineering
Investigator, Howard Hughes Medical Institute
Johns Hopkins University
Taekjip Ha analyzes single molecules to understand how they act in complex biological systems. Ha and his team combine sophisticated biophysical manipulation techniques with fluorescence imaging to visualize and manipulate protein, RNA, and DNA molecules. Probing these molecules allows the researchers to decipher such innate properties as a molecule’s “bendability” and how it binds and interacts with other molecules. Ha’s team strives to emulate or work within natural cellular environments while studying single molecules, testing diverse protein-nucleic acid and protein-protein interactions at unprecedented spatial and temporal resolution.
The Bioengineering Seminar Series is co-hosted by the Parker H. Petit Institute for Bioengineering and Bioscience, and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
NEW TWO-SPEAKER FORMAT for 2019-2020!
Seth Hutchinson, Ph.D.
Professor and KUKA Chair for Robotics
School of Interactive Computing
Executive Director of the Institute for Robotics and Intelligent Machines
Robots never know exactly where they are, what they see, or what they're doing. They live in dynamic environments, and must coexist with other, sometimes adversarial agents. Robots are nonlinear systems that can be underactuated, redundant, or constrained, giving rise to complicated problems in automatic control. Many of even the most fundamental computational problems in robotics are provably hard.
Over the years, these are the issues that have driven my group's research in robotics. Topics of our research include visual servo control, planning with uncertainty, pursuit-evasion games, as well as mainstream problems from path planning and computer vision. The links to the left will take you to pages that describe some of our results to date.
Gregory S. Sawicki, Ph.D.
George W. Woodruff School of Mechanical Engineering and
School of Biological Sciences
"A Bio-inspired Approach to Lower-limb Exoskeleton Design for Augmenting Human Locomotion"
Gregory Sawicki, Ph.D., directs the Human Physiology of Wearable Robotics (PoWeR) laboratory—where the goal is to combine tools from engineering, physiology and neuroscience to discover neuromechanical principles underpinning optimal locomotion performance and apply them to develop lower-limb robotic devices capable of improving both healthy and impaired human locomotion (e.g., for elite athletes, aging baby-boomers, post-stroke community ambulators).
By focusing on the human side of the human-machine interface, Sawicki and his group have begun to create a roadmap for the design of lower-limb robotic exoskeletons that are truly symbiotic---that is, wearable devices that work seamlessly in concert with the underlying physiological systems to facilitate the emergence of augmented human locomotion performance.
Sawicki is an Associate Professor at Georgia Tech with appointments in the School of Mechanical Engineering and the School of Biological Sciences. He holds a B.S. from Cornell University (’99) and a M.S. in Mechanical Engineering from University of California-Davis (’01).
Sawicki completed his Ph.D. in Human Neuromechanics at the University of Michigan, Ann-Arbor (‘07) and was an NIH-funded Post-Doctoral Fellow in Integrative Biology at Brown University (‘07-‘09). Sawicki was a faculty member in the Joint Department of Biomedical Engineering at NC State and UNC Chapel Hill from 2009-2017. In summer of 2017, he joined the faculty at Georgia Tech with appointments in Mechanical Engineering 3/4 and Biological Sciences 1/4.
Lydia Bourouiba, Ph.D.
Associate Professor, Civil and Environmental Engineering and Mechanical Engineering
Affiliate Faculty of the Institute for Medical Engineering and Science
Harvard-MIT Health Sciences and Technology (HST) Faculty
Affiliate Faculty of Harvard Medical School
Physical applied mathematician focusing on problems at the interface of fluid dynamics and disease transmission with the aim of elucidating the fundamental physical mechanisms shaping the epidemiology and disease transmission dynamics in human, animal and plant populations.
With a doctoral research focused on the theoretical and numerical study of rotating homogeneous turbulence and a subsequent postdoctoral research focused on the mathematical modeling of infectious diseases and epidemiology, the focus of the Bourouiba Group is to elucidate the poorly understood mechanisms of disease transmission through the lens of fluid dynamics.
The Bioengineering Seminar Series is co-hosted by the Parker H. Petit Institute for Bioengineering and Bioscience, and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
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.
For More Information Contact
A. Maureen Rouhi, Ph.D.
Director of Communications
College of 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)
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: email@example.com
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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
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.
Laurie Stevison, Ph.D.
Department of Biological Sciences
Stevison grew up just outside of New Orleans, LA. She earned a BS in Biophysics, a master's degree in the Ecology and Evolutionary Biology (EEB) Department at Rice University and completed her Ph.D. at Duke University. Her research there was broadly focused on the causes and consequences of recombination rate variation in Drosophila. In addition to building a dense recombination map in Drosophila persimilis and showing an indirect effect of male genotype on variation in female recombination, she worked with collaborators to perform one of the first population genomic studies using low-coverage whole-genome next generation sequencing, which answered long standing evolutionary questions in a classic model system for studying chromosomal inversions, Drosophila pseudoobscura and D. persimilis. Later, she performed a comprehensive analysis of inversions within and between species on their role in speciation in this system.
Host: Soojin Yi, Ph.D.
Aikaterini Kontrogianni-Konstantopoulos, Ph.D.
Department of Biochemistry and Molecular Biology
University of Maryland School of Medicine
Using the muscle and epithelial cells as model systems, my group has been studying the cytoskeleton as structural and signaling mediator in health and disease. This seminar will focus on the roles of two modular and multifaceted families of proteins the giant obscurins and their binding partner slow Myosin Binding Protein-C (sMyBP-C). Using complementary in vitro, ex vivo and in vivo approaches, we show that obscurins and sMyBP-C play key roles in filament assembly and stabilization, Ca2+ homeostasis, contractility, cell adhesion, and growth/survival pathways. Consistent with their involvement in several cellular processes, mutations in the OBSCN (encoding obscurins) and MYBPC1 (encoding sMyBP-C) genes have been causatively linked to severe and lethal diseases including skeletal and cardiac myopathies as well as cancer. We have therefore generated a number of disease models carrying truncated or mutant obscurins and sMyBP-C aiming to decipher the molecular and cellular alterations that lead to disease pathogenesis with the ultimate goal of designing new therapies in the form of rescue peptides and/or CRISPR technology.
Host: Yuhong Fan
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.