“I was raised a Yellow Jacket,” says Elizabeth Ann “Lizzie” Stubbs. She’s referring to her parents and grandfather, who all graduated from Georgia Tech. She knew all the cheers and chants by heart. But still, she wasn’t sure if Georgia Tech was where she should be. “Honestly, I was intimidated by Tech and I was very close to going to [the University of Georgia],” Stubbs says, afraid that she wouldn’t be able to maintain a high GPA.
But her mind changed one day. At an information session for students admitted to the College of Sciences, she asked a female student about her personal experience at Tech. The student assured Stubbs that it was possible to succeed at Tech. “I was sold,” Stubbs says.
Stubbs went to high school at Pinecrest Academy, in Cumming, Georgia. As the third oldest of seven siblings, she gained independence and a strong work ethic at an early age. These skills enabled her to work hard and succeed. Now she is graduating with a B.S. in Psychology, with a minor in Biology.
What is the most important thing you learned at Georgia Tech?
To believe in myself.
Georgia Tech is rigorous, as I expected. My biggest fear was that I wouldn’t succeed academically. But after my first semester, I proved to myself that I am capable, and that knowledge helped me get through some tough semesters. Tech has shown me time and again that I am capable of achieving my academic and other goals if I am willing to put in the work.
I also love the emphasis on innovation and research, which fosters progress and ignites people’s passions. I’m amazed to learn about the projects and inventions fellow students, faculty, and alumni are working on.
"Georgia Tech has prepared me well for the academic rigor and fast-paced atmosphere that I expect I will experience in PA [physician assistant] school. From conversations with alumni currently in PA school, I have learned that they were well-prepared because they had already established good study strategies, time management skills, and work ethic at Tech."
What are your proudest achievements at Georgia Tech?
One of my proudest achievements is receiving the Leddy Family Scholarship. I was honored to be recognized for my hard work, and it took a huge financial burden off my shoulders. I am incredibly grateful to Mr. and Mrs. Leddy for their generosity and support.
It was awesome to learn that a paper of my research group was accepted for publication in the Journal of Autism and Developmental Disorders. I was listed as a coauthor for data analysis. The study we reported assessed the eye contact behavior of typically developing children versus children diagnosed with Autism Spectrum Disorder during play and conversation segments.
Which professors or classes made a big impact on you?
I loved Human Anatomy, a class taught by Adam Decker. I loved reading the textbook, and studying the material. I found the information so fascinating, and it helped confirm my decision to study medicine. That class was a lot of work, but Decker always kept lectures lively and informative.
What is your most vivid memory of Georgia Tech?
The Aug. 21, 2017, solar eclipse.
It was awesome to see students, faculty, and staff admiring and enjoying this rare occurrence all out on Tech Green. We were all just geeking out together and it was awesome!
How did Georgia Tech transform your life?
Tech helped shape the path that I am on and helped me grow as a person.
I volunteered to do outreach through programs like Hands on Future Tech and Step into STEM (science, technology, engineering, and mathematics).
This past winter break I went on a medical mission with Volunteers Around the World. We traveled to the Dominican Republic and set up mobile clinics in various villages. It was such an incredible experience, and I plan to continue going on medical missions and finding ways to serve those most in need.
Being involved in research since my second year has been one of the greatest things I about my time here.
Each of these opportunities required me to step outside of my comfort zone. I grew and learned valuable skills.
What unique learning activities did you undertake?
I never planned on doing research because I didn’t think I would enjoy it. But an older student told me about the lab she worked in and I was intrigued. After touring the Child Study Lab, I knew I was meant to work there.
Working at the Child Study Lab, with Agata Rozga of the School of Interactive Computing, is one of my best experiences at Tech. The lab is also one of the best work environments I’ve encountered. Working in this lab for three years now has helped me grow. It taught about psychology and research in general. I learned a lot about myself. By stepping outside of my comfort zone, I gained confidence.
What advice would you give to incoming undergraduate students at Georgia Tech?
Yes, Tech is hard, but you are more than capable of succeeding if you put in the work.
Do the homework, study the material outside of class time, and get help if you need it. Be confident in your skills and abilities. That you were accepted into Tech means you have the ability to excel here.
Step outside of their comfort zone and try new things. You will gain valuable experiences and learn about yourself along the way.
Where are you headed after graduation?
I will take a gap year, working as a medical assistant to gain patient care hours before going back to physician assistant (PA) school. Georgia Tech has prepared me well for the academic rigor and fast-paced atmosphere that I expect I will experience in PA school. From conversations with alumni currently in PA school, I have learned that they were well-prepared because they had already established good study strategies, time management skills, and work ethic at Tech.
By the time Libby Taylor graduated from Wheeler High School, she had already completed her freshman and sophomore years at Georgia Tech. Beginning as a junior may be daunting to some, but because the Marietta, Georgia, native already knew that she loves Tech, deciding to stay for two more years came easily. This untraditional path began during her sophomore year of high school, when she took calculus through Georgia Tech’s Distance Math program. The next year, she signed up as a full-time dual-enrolment student.
Wheeler’s science, technology, engineering, and mathematics (STEM) magnet program allowed Taylor to immerse herself in science and mathematics. Originally, she planned to major in chemistry, but once on campus she gravitated to mathematics.
Her extraordinary mathematical talents were recognized earlier this year by the Association for Women in Mathematics, which awarded Taylor the 2018 Alice T. Schafer Mathematics Prize. Now, only two years after high school, she’s graduating with a B.S. in Mathematics
What is the most important thing you learned at Georgia Tech?
The most important thing I learned at Georgia Tech is that professors do not bite. Seriously, most students think that professors are intimidating. In my experience, that has never been the case. All the professors I've interacted with have been incredibly nice people and have been more than willing to help with any questions I've had, including the really dumb questions.
One way that Georgia Tech surpassed my expectations was in how hard the students here work. People are very motivated to learn, and they're willing to put in a lot of work to get where they want to be.
"My most vivid memory is the time I solved my first research problem. I had been close to a solution for a couple of days, and when I finally put the pieces together, it was while I was out buying groceries!"
What are your proudest achievements at Georgia Tech?
Probably winning the 2018 Alice T. Schafer prize. That prize was a great honor. It validated both the work I had put into my career and the contributions of the professors who advised me along the way.
Which professors or classes made a big impact on you?
In my senior year of high school, I took math courses from Matt Baker and Tom Trotter. Because of their mentorship, I discovered my love of mathematics and began my first research projects that same year. Their guidance throughout the past three years has been invaluable and has been a major component in my being accepted to graduate school at Stanford, which has always been one of my dream schools.
Although I have never taken a class from Christine Heitsch, she has given me a lot of good advice, both for professional development and for life in general.
Padma Srinivasan, who taught my algebraic number theory class, was a big factor in my decision to study number theory in graduate school. Her enthusiasm for number theory and arithmetic geometry have proved contagious, and she has been a great resource for mathematics, as well as a great friend.
What is your most vivid memory of Georgia Tech?
My most vivid memory is the time I solved my first research problem. I had been close to a solution for a couple of days, and when I finally put the pieces together, it was while I was out buying groceries!
I didn't have a proper notebook to write the solution, so I pulled a pack of stickie notes out of my purse and wrote a proof on those. That stickie-note proof turned into my first paper.
How did Georgia Tech transform your life?
When I started at Georgia Tech, I didn't really know what I wanted to study; I was considering chemistry, physics, or economics. It was in my second year at Georgia Tech that I realized I loved mathematics, and I hit the ground running after that.
What unique learning activities did you undertake?
I did a study abroad in China the summer after my second year. It gave me a chance to see a part of the world that I would never have gotten to see so much of otherwise, and it threw me into an environment where I was forced to be uncomfortable.
I improved my Chinese language skills a lot by necessity, and I got a chance to navigate in a country with which I was entirely unfamiliar. Some of my favorite memories (and best stories!) from Georgia Tech came from that trip.
What advice would you give to incoming undergraduate students at Georgia Tech?
Go to your professors’ office hours! Even if you aren't struggling in the class, go anyway to chat about course material. You’ll learn a lot from those conversations, and you will probably come away with a much deeper understanding of what’s being covered in class and why it’s important.
Where are you headed after graduation? How did your Georgia Tech education prepare you for this next step?
I am headed to Stanford to pursue my Ph.D. in Mathematics. Georgia Tech has prepared me very well for graduate school by giving me a chance to get research experience, take graduate courses, and present at conferences, all of which are crucial skills for graduate school.
The Georgia Institute of Technology will hold its 255th Commencement ceremonies on May 4-5, 2018, at McCamish Pavilion on the Georgia Tech campus.
College of Sciences' alumnae will address the master's ceremony and the first of two bachelor's ceremonies.
The master’s ceremony is scheduled for 3-5:30 p.m. on May 4; doors open at 1:30 p.m.
Valerie Montgomery Rice, Georgia Tech alumna and president and dean of the Morehouse School of Medicine, will deliver the keynote address. Rice is the sixth president of the Morehouse School of Medicine and the first woman to lead the free-standing medical institution.
She is a renowned infertility specialist and researcher and has served as the dean of the School of Medicine and senior vice president of health affairs at Meharry Medical College, where she founded and directed the Center for Women’s Health Research. She earned a degree in chemistry from Georgia Tech and her medical degree from Harvard Medical School.
The two bachelor’s ceremonies are scheduled for May 5. The morning ceremony will run from 9 to 11:30 a.m. Georgia Tech alumna and former astronaut Jan Davis will deliver the keynote address. Davis earned a degree in applied biology from Georgia Tech before going on to complete a bachelor of science degree in mechanical engineering at Auburn University. She earned her master’s and her doctorate in mechanical engineering from the University of Alabama in Huntsville.
During her career at the National Aeronautics and Space Administration (NASA), she provided technical support for space shuttle payloads, served as the capsule communicator on seven missions and logged more than 673 hours in space on three space flights.
This ceremony includes the following academic disciplines:
- College of Computing: Computer Science
- College of Design: Industrial Design and Architecture
- College of Sciences: Psychology, Discrete Mathematics, Applied Mathematics, Earth and Atmospheric Sciences, and Biology
- College of Engineering: Environmental, Civil, Biomedical, Materials Science and Engineering, Industrial, and Aerospace.
More than 2,120 undergraduates will receive bachelor’s degrees. The master’s ceremony will award 1,370 master’s degrees and the Ph.D. ceremony will award 180 doctorates.
EDITOR'S NOTE: This item was excerpted from a story by Lance Wallace, published on March 29, 2018, in the Georgia Tech News Center.
When Amy Lynn Williamson moved to Georgia to attend Georgia Tech, it was the first time she had ever moved from Ohio, where most of her family lives. She completed her B.S. in Geosciences at Denison University, in Granville, a small town close to home. For Williamson, the move to Midtown Atlanta was a big step.
But she couldn’t resist the draw of Georgia Tech. “I was attracted to Georgia Tech because of its close-knit geophysics department,” Williamson says, “Even though Georgia Tech is a large research-oriented institute, EAS [School of Earth and Atmospheric Sciences] maintains a small and supportive environment.” Interdepartmental group meetings, yearly student symposia, and a graduate student activity group are some features of EAS that, she says, made her feel part of the community.
Williamson is receiving a Ph.D. in Earth and Atmospheric Sciences.
What is the most important thing you learned at Georgia Tech?
Georgia Tech taught me not only how to conduct research but also how to communicate it to a wider audience. In the research group of Andrew Newman, everyone worked on the same broad topics but each one had distinct research projects. This means constantly presenting and discussing our work and learning about everyone else’s projects. I had opportunities to present my research in small group meetings and in domestic and international conferences.
Georgia Tech and EAS were helpful every step of the way, from travel to large conferences to facilitating small symposia and events in the school.
"Georgia Tech and the School of Earth and Atmospheric Sciences were helpful every step of the way, from travel to large conferences to facilitating small symposia and events in the school."
What is your proudest achievement at Georgia Tech?
Defending my Ph.D. dissertation.
Not only am I in the first generation of my family to attend college, but I also will be the first person in my family to hold a doctorate degree.
What is your most vivid memory of Georgia Tech?
The hours spent in the gym with my groupmate discussing research and getting in shape to prepare for lugging instruments up the side of Costa Rica’s Arenal Volcano.
Who knew that lunges and talks about crustal deformation would mix?
What unique learning activities did you undertake?
During my first summer, I joined a research cruise to retrieve ocean bottom seismometers from off the coast of Vancouver Island. This experience showed me the breadth of research in seismology and geodesy. It was also my first to be on a research ship, and – given my new-found knowledge of sea sickness – it might be my last.
Midway through my Ph.D., I participated in a research-abroad program hosted by the National Science Foundation and the Australian Academy of Sciences. The program allowed me to work with new research collaborators in Canberra, Australia.
During this trip, I gained new perspective about my research by interacting with research groups that I otherwise would have interacted with only occasionally. I also experienced living and working abroad and the surreal situation of having a mob of kangaroos live right outside my front door.
What advice would you give to incoming graduate students at Georgia Tech?
Be involved in the greater Atlanta community. Get involved in outreach related to your field, attend events off campus, and make Atlanta more like a home, and not just a place where you work and study.
Even though I love Georgia Tech, it was great to get off campus, explore, and meet new people. I did this through running, with the local running club. Keeping up with a hobby off campus also helps manage the stressful moments during graduate studies.
Where are you headed after graduation?
I am headed to the University of Oregon where I will be a postdoctoral researcher focusing on tsunami hazards for the Pacific Northwest. My studies in the Newman research group helped me prepare for this role. Even though my dissertation topic and my future work in Oregon focus on a field that is not currently a major research area in Georgia Tech, my advisor has been incredibly helpful.
Cancer drops sparse chemical hints of its presence early on, but unfortunately, many of them are in a class of biochemicals that could not be detected thoroughly, until now.
Researchers at the Georgia Institute of Technology have engineered a chemical trap that exhaustively catches what are called glycoproteins, including minuscule traces that have previously escaped detection.
Glycoproteins are protein molecules bonded with sugar molecules, and they’re very common in all living things. Glycoproteins come in myriad varieties and sizes and make up important cell structures like cell receptors. They also wander around our bodies in secretions like mucus or hormones.
But some glycoproteins are very, very rare and can serve as an early signal, or biomarker, indicating there’s something wrong in the body – like cancer. Existing methods to reel in glycoproteins for laboratory examination are relatively new and have had big holes in their nets, so many of these molecules, especially those very rare ones produced by cancer, have tended to slip by.
Cancerous traces
“These tiny traces are critically important for early disease detection,” said principal investigator Ronghu Wu, a professor in Georgia Tech’s School of Chemistry and Biochemistry. “When cancer is just getting started, aberrant glycoproteins are produced and secreted into body fluids such as blood and urine. Often their abundances are extremely low, but catching them is urgent.”
This new chemical trap, which took Georgia Tech chemists several years to develop and is based on a boronic acid, has proven extremely effective in lab tests including on cultured human cells and mouse tissue samples.
“This method is very universal,” said first author Haopeng Xiao, a graduate research assistant. “We get over 1,000 glycoproteins in a really small lab sample.”
In comparison tests with existing methods, the chemical trap, a complex molecular construction reminiscent of an octopus, captured exponentially more glycoproteins, especially more of those trace glycoproteins.
Wu, Xiao and Weixuan Chen, a former Georgia Tech postdoctoral researcher, who was also first author of the study alongside Xiao, published their results in the journal Nature Communications. The research was funded by the National Science Foundation and the National Institutes of Health.
Boronic bungles
For chemistry whizzes, here’s a short summary of how the researchers made the octopus. They took a good thing and doubled then tripled down on it.
Those who recall high school chemistry class may still know what boric acid is, as do people who use it to kill roaches. Its chemical structure is an atom of boron bonded with three hydroxyl groups (H3BO3).
Boronic acids are a family of organic compounds that build on boric acid. There are many members of the boronic acid family, and they tend to bond well with glycoproteins, but their bonds can be less reliable than needed.
“Most boronic acids let too many low-abundance glycoproteins get away,” Wu said. “They can catch glycoproteins that are in high abundance but not those in low abundance, the ones that tell us more valuable things about cell development or about human disease.”
Benzoboroxole octopus
But the Georgia Tech chemists were able to leverage the strengths of boronic acids to develop a glycoprotein capturing method that works exceptionally well.
First, they tested several boronic acid derivatives and found that one called benzoboroxole strongly bound with each sugar component on the glycopeptide. (“Peptide” refers to the basic chemical composition of a protein.)
Then they stitched many benzoboroxole molecules together with other components to form a "dendrimer," which refers to the resulting branch- or tentacle-like structure. The finished large molecule resembled an octopus ready to go after those sugar components.
In its middle, similarly positioned to an octopus's head, was a magnetic bead, which acted as a kind of handle. Once the dendrimer caught a glycoprotein, the researchers used a magnet to grab the bead and pull out their chemical octopus along with its ensnared glycopeptides (e.g. glycoproteins).
“Then we washed the dendrimer off with a low pH solution, and we had the glycoproteins analyzed with things like mass spectrometry,” Wu said.
Cancer treatments?
The researchers have some ideas about how medical laboratory researchers could make practical use of the new Georgia Tech method to detect odd biomolecules emitted by cancer, such as antigens. For example, the chemical octopus could improve detection of prostate-specific antigens (PSA) in prostate cancer screenings.
“PSA is a glycoprotein. Right now, if the level is very high, we know that the patient may have cancer, and if it’s very low, we know cancer is not likely,” Wu said. “But there is a gray area in between, and this method could lead to much more detailed information in that gray area.”
The researchers also believe that developers could leverage the chemical invention to produce targeted cancer treatments. Immune cells could be trained to recognize the aberrant glycoproteins, track down their source cancer cells in the body and kill them.
The research’s potential for science goes far beyond its possible future medical applications.
The fields of genomics and proteomics have made great strides. Following in their footsteps, this new molecular trap could advance the study of the rising field of glycoscience.
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ALSO read: Cancer-killing T-cells switched on via remote control
Georgia Tech’s Johanna Smeekens coauthored the research paper. The research was funded by the National Science Foundation (CAREER award CHE-1454501), and the National Institutes of Health (R01GM118803). Findings and any opinions are those of the authors’ and not necessarily of the funding agencies.
By Mallory Rosten, Student Communications Assistant, College of Sciences
School of Biological Sciences Professor Emeritus Phillip Sparling has published his first book of creative nonfiction. “The Sneakers in the Closet and Other Essays” explores the intersection of sports, health, and life. It’s a collection of 24 stories (and a few poems), compiled and re-edited, from newspaper columns Sparling wrote over several years.
In the eponymous first essay, Sparling reminisces on a childhood full of sports and physical activity. As a kid, he was constantly on the move, taking detours from bicycling to school to climb trees or scale a wall. He can measure the phases of his youth by sports: four square and kickball in elementary school; neighborhood pickup games of football, basketball, and baseball through junior high school; and then cross-country and track in high school. .
Maybe that’s why Sparling dedicated his research to unraveling connections between fitness and health. His early research focused on investigating relationships among endurance training, resistance training, energy balance, body composition, and cardiovascular health. In the mid-1990s, his research shifted to understanding physical activity and eating patterns as modifiable health behaviors.
Sparling joined Georgia Tech in 1979 as an assistant professor in what was then the Department of Physical Education. When he retired almost 30 years later, it had become the School of Applied Physiology, which merged with the School of Biology to form the School of Biological Sciences in summer 2016. During his last decade at Tech, Sparling taught a large lecture “Personal Health” course and the graduate-level courses “Exercise Physiology” and “Physical Activity and Health.”
In retirement, Sparling broadened his writing to include narrative nonfiction. “It allows more creativity than scientific and technical writing,” Sparling says. He began publishing essays in Smoke Signals, the local paper of Big Canoe, a mountain community about one hour north of Atlanta. His editor and friends encouraged him to publish the essays in a book. In “The Sneakers in the Closet and Other Essays,” he reflects on various topics – from play, exercise, and fitness to diet, drugs, and doctors.
“My aim is to engage and educate by sharing stories, including personal reflections on growing up, finding a career and growing older,” Sparling says, “and to show how role models shape our health and well-being.” He hopes that people who read his stories walk away “better informed, empowered, and thankful.”
The book’s proceeds go to the Richard Gay Israel Health and Exercise Science Scholarship at Colorado State University. Sparling describes his late colleague, Richard Gay Israel, as “salt-of-the-earth and a natural leader.”
At Georgia Tech, Sparling expanded the study of health and exercise by establishing and directing the Exercise Physiology Laboratory, developing the Ph.D. program in applied physiology, and advocating for the integration of behavioral science with biomedical science. For a decade, he served as chair of Georgia Tech’s Institutional Review Board for the protection of human subjects in research.
Sparling also had sabbatical experiences as a senior scientist with the Centers for Disease Control and Prevention and a Fulbright Scholar at University of Cape Town Medical School, in South Africa. In addition, Sparling was a leader in professional societies, including the American College of Sports Medicine and the Society of Behavioral Medicine.
“I'm proud to have spent my career at Georgia Tech – a top-notch institution with excellent students, staff, and faculty,” Sparling says.
In addition to writing and reading, Sparling gardens and hikes with his wife, Phyllis, in the Georgia foothills where they live. They enjoy travel at home and abroad. And he continues to write columns to nudge folks to healthier ways and a fuller life.
Using an informatics tool that identifies “hotspots” of post-translational modification (PTM) activity on proteins, researchers have found a previously-unknown mechanism that puts the brakes on an important cell signaling process involving the G proteins found in most living organisms.
The mechanism, dubbed a “tail,” is part of a small protein known mostly for its role in attaching larger structures to the cell membrane. When researchers inactivated the tail, a signaling response that had previously taken 30 minutes to occur happened almost immediately – with an intensity four times greater than normal.
The research took place in yeast, but if a similar process occurs in human G proteins, the discovery could provide a new drug target for controlling important cellular processes – and potentially offer a new class of biosensors able to more sensitively detect and respond to certain chemical agents. The research, supported by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS), was reported May 1 in the journal Cell Reports.
“We have discovered the mechanism that regulates how quickly a pathway gets turned on by an external stimulus,” said Matthew Torres, an associate professor in the School of Biological Sciences at the Georgia Institute of Technology. “By genetically altering the control mechanism underlying this process, we are able to modulate how much of a signal from outside the cell gets inside the cell and how quickly it gets through. It’s all the more astonishing because this mechanism has been hiding in plain sight for decades.”
G proteins, also known as guanine nucleotide-binding proteins, are a family of molecules that operate as molecular switches inside cells. They transmit signals acquired from a variety of extracellular stimuli to the interior of a cell – through the membrane, which otherwise wouldn’t allow communication.
The tail found by Torres and Doctoral Candidate Shilpa Choudhury likely escaped attention because it is flexibly attached to the G protein gamma subunit of a closely-collaborating protein team known as G beta/gamma. Protein structures have generally been identified by X-ray crystallography techniques which cannot resolve structures that are in motion.
Prior to their work, the G gamma subunit has been known primarily as the protein that connects the larger G beta subunit to the cell membrane. Without the work of SAPH-ire – an informatics program that maps PTM activity using machine learning – the role of the tail structure might not have been identified.
“For years, people had focused on G beta/gamma as a complete unit, and not as separate components,” said Choudhury, the paper’s first author. “The gamma is a tiny protein compared to the larger G beta subunit, but we now know that it has a major role in the activity of the signaling system.”
In yeast, G beta/gamma subunits activate a signaling pathway in response to pheromones, a process which normally takes about 30 minutes after stimulation of a pheromone receptor at the cell membrane. Torres and Choudhury suspected that protein modifications, PTMs, were somehow causing the delay. Their computer program SAPH-ire – developed in the Torres lab and announced in 2015 – pointed the finger straight at the G gamma subunit.
The program analyzes existing meta-data repositories of protein sequence and PTM activity to reveal “hotspots” of protein alteration. SAPH-ire was designed to accelerate the search for important regulatory targets on protein structures and to provide a better understanding of how proteins communicate with one another inside cells.
Pulling from worldwide PTM databases that use mass spectrometry to identify sequences that are chemically altered, SAPH-ire pointed to a specific location on the G gamma protein. Using genetic mutation techniques, Choudhury modified a section of the protein to render the tail structure inactive.
But removing the tail from the process by itself wasn’t enough. To activate the signaling process, structures on the tail had to interact with a separate effector protein. When both were inactivated, the researchers saw a dramatic effect when the receptor was stimulated.
“You can think of the signaling pathway like a wheel travelling down a hill where two pads of the bicycle brake are gripping the wheel to slow it down,” said Torres. “Activating the pheromone receptor is like releasing the wheel down the hill. When both brakes are active, the wheel moves very slowly because the two brakes are working together to slow its speed and momentum. This turns out to be how the pathway behaves in normal cells immediately after receptor stimulation.”
“If you take away one of the brakes, you get partial braking and the wheel is allowed to move slightly faster, but is still restrained from moving as fast as it can. This is how the pathway behaves in normal cells within the first 20 minutes after receptor stimulation. But if you eliminate both brakes, releasing the wheel down the hill results in very high speed and momentum – kind of like a golf cart without a governor.”
This is exactly what happened when Choudhury prevented PTMs on both G gamma and the effector protein. “When we do that, we see a rapid activation of the signaling pathway that occurs six times faster, and is four times more intense than with the normal condition with the pathway brakes intact.”
Beyond identifying the control mechanism for the pathway, the researchers also learned how it controls the ability of yeast to respond to pheromones in a “switch-like” manner that is either on or off versus an analog manner that is analogous to a volume knob on a stereo.
While Torres and Choudhury made their discovery in yeast, they believe it will have broad implications because all organisms that have G proteins, including humans, have G gamma tails that are riddled with PTMs. Among the next steps will be to see if the same type of braking system is exhibited by G gamma subunits and G beta/gamma effectors in human cells. If so, that could provide insights that could identify potentially new drug targets.
“The tail exists, and it’s important in this process of controlling interactions with G beta/gamma effectors, which are essential for turning on signaling pathways,” Torres said. “We suspect the importance of G gamma as a regulator G protein signaling will extend beyond any single organism.”
This research was supported by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS) grants R01GM117400 and R00GM094533. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
CITATION: Shilpa Choudhury, Parastoo Baradaran-Mashinchi and Matthew Torres, “Negative Feedback Phosphorylation of Gy Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast,” (Cell Reports, 2018). https://doi.org/10.1016/j.celrep.2018.03.135
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New degree programs. More undergraduate admissions. Participation in Nobel Prize-winning research. A Tech Green solar eclipse watch party.
Paul Goldbart's five years as the Dean of the College of Sciences were highlighted by changes, growth, community-building, and opportunities. Goldbart, the College's Betsy Middleton and John Clark Sutherland Chair, talks about his time at Georgia Tech in this first installment of a two-part audio story that also serves as a preview for the forthcoming College of Sciences podcast, ScienceMatters.
This audio story is hosted and produced by College of Sciences Communications Officer Renay San Miguel. You can listen to the story by clicking on the image link to the right, or you can read the transcript below.
Part 2 will be available on May 16, 2018.
If you want to know more about ScienceMatters, click here.
Renay San Miguel: Hello. I’m Renay San Miguel with the Georgia Tech College of Sciences. By now, you may have learned that College of Sciences Dean Paul Goldbart has accepted a position to be the next dean of the College of Natural Sciences in the University of Texas at Austin. The Lone Star State’s gain is our loss. We are sad to see Paul go, and we thank him for his extraordinary service to the College of Sciences and to Georgia Tech.
I interviewed Paul in early 2018 for the premier episode of the College of Sciences’ podcast called “ScienceMatters.” With the new appointment in Texas, however, we’ve recast the interview into a two-part audio story to serve as a valedictory for Paul, as well as a preview of “ScienceMatters,” which will begin broadcasting later in 2018.
Here is Dean Paul Goldbart in his own words, and you can hear him as both engaging physics professor and forward-thinking administrator as he charts opportunities for growth of the Georgia Tech College of Sciences, and recalls the highlights of his tenure.
Essential, exciting research in astrobiology
Paul Goldbart: So let me begin with astrobiology. Once upon a time, that title sounded like a crank science. It’s really moved to center stage now, incredibly exciting. So we have folks really thinking about how to search for life in space and in time, looking out into the cosmos. Wouldn’t it be remarkable to find out where our neighboring colonies of life are? And we have communities looking at that from the aspects of biology and chemistry, from Earth and atmospheric sciences, and physics. We have people thinking about exoplanets, how you find and discover the properties of planets orbiting other stars. So tremendous range and tremendous interdisciplinarity.
We also have folks who are looking back in time. How did life start here on Earth? Wonderful activities in chemistry, Earth and atmospheric science and biology, looking at this tiny, thin sliver of a shell of life here on our remarkable planet, and people essentially doing the archaeology of the oceans: What was the chemical composition of the oceans back in time? Was there enough oxygen to sustain life? Folks working on that kind of really fundamental and incredibly exciting question.
So astrobiology is really central, and we have a thriving community. And it reaches out well beyond the College of Sciences—interacting with folks in the Ivan Allen College of the Humanities—wonderful community there and elsewhere on campus, too. So delighted to see that here at Georgia Tech.
Essential exciting research in microbial ecology
Let me turn to another area in the life sciences that I’m very excited about: the area of microbial ecology. There are microbes everywhere, all around us, and we live in this, hopefully, symbiotic relationship with them. And the study of microbial ecology is really taking shape quite wonderfully here with an emerging community of people from biological sciences, from chemistry, and from physics. And this subject needs tools all the way from genetics and biology, through game theory, physics and mathematics, all the way into medicine.
So just to give you a flavor of the subject how microbes, and then microbial infections, infect us, harm us, is really a question of the shape and structure of the colonies that they form. And so physicists are teaming up with biologists to understand the kind of materials that form through microbial infections. And this is taking us all the way from basic science through to wound care and all the way to healthcare and cystic fibrosis. So I must say, from my perspective, it’s incredibly exciting to see science, both at the fundamental level, but also reaching out into the community.
Renay San Miguel: And so many applications for what is being researched here. You know, as we have this conversation, we’re going through one of the worst flu epidemics that the country has seen in a long time and—but there are so many things that this would be applied to, you know, to warfare and treating wounds in battlefield, things like that. It’s just very exciting research.
Paul Goldbart: That’s right. And healthcare within hospitals — microbial infections arise in hospitals at an enormous rate. And so what’s so exciting is to look at this long arc of history and feel that we are the tip of the sphere and that the sphere, currently, in developing new knowledge and understanding to inform the healthcare of the future, and that’s a remarkable, remarkable place to be.
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Welcoming students with a celestial event
Renay San Miguel: Let’s talk about the eclipse.
[Applause and cheering]
Renay San Miguel: On August 21st, 2017, the first day of classes, thousands of members of the Georgia Tech community descended on Tech Green to watch the moon’s shadow cover 97 percent of the afternoon sun.
Georgia Tech student: I will always remember this because I saw the eclipse and started college on the same day at the best university.
Paul Goldbart: College of Sciences along with the Provost’s office put together a quite exquisite array of activities. Those of you who live in the Southeast might know of Woodstock, Georgia. This was a different kind of Woodstock. This was a remarkable event on campus.
We had thousands and thousands of people coming together, congregating, all inspired by an eclipse. And eclipses, of course, go back in history and they’ve had quite interesting sociological impacts ushering in new eras and so forth. And so to watch our community come and react—our community of scientists and mathematicians and technologists and engineers and others come together, but react in this wonderfully human way and enjoy this remarkable astronomical event was really wonderful.
And so just to see the community out there with this festival atmosphere was great. And the only concern, really, is what are we going to do next year? Really, it was a marvelous time.
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Helping to prove Einstein was right
Renay San Miguel: Tell me about gravitational waves. I mean the idea of the institute and some of the faculty and the researchers and students here involved in what would eventually be a Nobel Prize-winning effort had to be just so pleasing for you.
Paul Goldbart: Well this is very exciting. So I’ve been at Georgia Tech for about seven years, and astrophysics was launched here a little bit before I arrived and has really taken root quite beautifully with wonderful leadership initially from Pablo Laguna and now from Deidre Shoemaker.
But let me tell you a little bit about the story because the story really goes back now a little bit over 100 years: Albert Einstein has put together his masterpiece theory of what’s called “general relativity,” which is really the first successful post-Newtonian understanding of gravity.
And the remarkable shift in thinking that came about with Einstein in 1915 was the idea that space and time, themselves, have a kind of pliability or elasticity to them; they’re not just a rigid stage on which the history of the universe unfolds. But, they are, in their motions and changes, part of that story; they are actually actors, not just the stage.
And one of the predictions goes something like this: You may know that if you shake an electrical charge, out comes electromagnetic radiation. That, for example, is how when you heat an atom, it puffs off a little bit of light; that’s where we get the yellow of sodium lamps, for example. So shaking, charges. Electrical charges cause a ripple in the electromagnetic field that propagates outward, and that’s what we call light or, in other frequencies, different forms of radiation like X-rays or infrared radiation, just to give two examples.
After Einstein in 1915, we understood that the same kind of thing happens with mass. If you shake some mass somewhere in the universe, that mass actually causes a ripple. But now the ripple is not in the electromagnetic field, but it’s in space and time—the actual geometry of space and time themselves—and that ripple propagates out, and it takes a certain amount of time to arrive at a distance.
So, for example, if the sun were to magically disappear, we wouldn’t know it for the eight or so minutes that it would take for the gravitational field to change and respond to a new configuration, the one that would be there in the absence of the sun, at which time the planet, Earth, would fly off in a kind of tangential trajectory rather than its almost circular orbit.
Ripples through time and space
So the basic idea is that masses, when they move and they accelerate, they can give rise to a rippling in space and time that propagates like a wave, like the ripples that you find on the surface of a pond when you throw a stone in. The tough part of the story is that space and time are remarkably stiff, and so it takes very big masses to have a perceptible, measurable impact.
And where can you find big masses accelerating quickly? Well, you can find them in the mergers of black holes. So I remind you that black holes are stars that have collapsed under gravity so much so, that not even light, essentially, not even light can escape from them; that’s why they’re black.
They’re very, very dense objects. And they can come, occasionally, in pairs and they orbit around one another in the same way, roughly speaking, that the moon orbits around the Earth.
Now what happens is that these two black holes are moving around one another and, because of this idea of space and time having a kind of elasticity to them, that binary black hole system radiates out energy in the form of gravitational waves. And just a little bit like the yolks of two eggs frying in a frying pan, they move around one another and, eventually, in this cataclysmic event, they merge into a single yolk. Here, they merge into a single black hole, and as they do, they give out an astonishing amount of energy in the form of gravitational radiation which then propagates through the cosmos and that’s the way it goes—until LIGO.
Large instruments looking for small moves
And LIGO is this experiment, this collaboration—roughly 1,000 people working hand-in-glove, two stations: Hanford, Washington, and Livingston, Louisiana, and there are experiments at both sites. And the reason there are two sites is that you want to understand coincidence. If a gravitational wave passes through one and then passes through the other, you know far they are apart and you know how long that ought to take, and you can really have a chance of finding the needle in the proverbial haystack of these very, very small signals.
So the experiment has been in the making for several decades, fantastic support from the federal government even though this is an incredibly challenging experiment to undertake, and I applaud the citizens of the United States for supporting this really heroic endeavor which, I think, is as much part of culture as it is a part of technology and science.
So the experiment goes like this: You have to detect this wave coming through. And what does the wave do? Well, it changes the shape of space and time, but it does so at a very small level. And just to give you a sense of the smallness of the changes that have to be detected, let me ask you to look at your pinkie. Look at your little finger and ask, how broad is the nail? Well, roughly speaking, it’s about a centimeter across, something like that. Now shrink down by about 8 powers of 10—so about 100 million— and that gets you to about the size of an atom—not enough. Now go down by another 8 powers of 10.
That gets you to about the size of a nucleus of an atom, but smaller: about a thousandth of the size of the nucleus of an atom. And that is the distance, or change in separation, between the detectors of the experiment in an evacuated tube about four kilometers long—one in Louisiana, one in Washington—that needed to be detected. Quite a challenge.
I’m told that it’s as if we knew the distance from Earth to the nearest star to within the thickness of a human hair.
Renay San Miguel: No! [Chuckles]
Paul Goldbart: I haven’t checked that calculation but it sounds a bit right to me. Quite a challenge. And this, nevertheless, was accomplished. Not only was it accomplished, but it was accomplished the day after the experiment was turned on — 20 years in the making. And it’s as if nature had conspired to send us this perfect signal.
Renay San Miguel: It was just waiting for us to build these instruments.
Paul Goldbart: Exactly. “Are you ready? Are you ready?” [Laughter] So to give you a sense of scale, the gravitational event, the merger of two black holes that was detected about two and a half years ago, and that wave has been propagating through space, waiting, [laughter] and arriving here at Earth to be detected.
Now, since then—and we say in science sometimes “Yesterday’s sensation, today’s calibration”—that event is one of several that have now been detected; it’s raining black hole mergers out there. And the most recent event, another truly stunning event much closer to Earth, was the signature of the collision—not now of two black holes, but of two neutron stars.
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Renay San Miguel: And that particular celestial collision would result in another major breakthrough for College of Science researchers. That, along with Paul Goldbart’s vision for the future of the College of Sciences, is coming up in Part 2 of this audio story. I’m Renay San Miguel with the Georgia Tech College of Sciences.
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Through viewing vacation pictures, we can relive the scorching heat of the sand on the beach, the smell of sun block slathered all over our skin, and the cool breeze kissing our face as we take lazy bicycle rides just when the sun is disappearing from the horizon. Vacation pictures might also remind us of details that have nothing to do with a specific experience. For example, the picture of the bicycle ride might remind me that dusk is my favorite time of day.
These reminiscences are called autobiographical memories. They can be episodic, referring to experiences of events, or semantic, referring to personally relevant information that transcends any specific event.
“Autobiographical memories are the mind’s record of our daily life,” says Thackery Brown, an assistant professor in the School of Psychology. “These memories help define the very nature of who we are. Knowing how these distinct memories are processed differently across the brain can help us understand why we remember – or fail to remember – our lives with different degrees of detail.”
In a recent study published in Scientific Reports, Brown and others advanced our understanding of autobiographical memories. Using brain imaging and an innovative memory test using images from people’s actual lives, they have shown that different regions of the brain process episodic and semantic autobiographical memories differently.
The findings open a window into the brain processes that give rise to memories with different degrees of detail. “This knowledge can help us understand what memory impairments to expect from different types of brain damage,” Brown says. “They advance our understanding how factors such as aging and disease can affect what we remember from our lives,” Brown says. “For example, when aging impacts some areas of the brain more than others, our ability to remember facts from our lives in a general way could be left intact, but our ability to vividly relive details of an experience could be impaired.”
The findings may have other relevance, such as in the use of neuroscience methods in lie detection or in evaluating the accuracy of courtroom testimony.
“To study how memory works – and to ask questions like ‘How vivid is a memory?’ – our lab and others use tools from computer science and machine learning to get a read-out from patterns of brain activity for signatures of the type of information people are remembering,” Brown says. “But these techniques have limitations, which we need to understand before they are used to, for example, support a criminal conviction.”
In fact the findings suggest that the ability to discriminate between semantic (dusk is my favorite time of day) and episodic (the sand was scorching that particular day on the beach) memories may be limited. “However, our work identifies areas of the brain where this distinction can be made,” Brown says. “Therefore, this study helps focus our lens on the brain regions where the different types of memories be teased apart with brain imaging.”
INNOVATIVE EXPERIMENTAL DESIGN
According to Brown, many laboratory studies of memory are limited in their ability to reveal the brain processes involved specifically in autobiographical memories because they require participants to create memories in the laboratory from experimental stimuli -- such as pictures, words, or sounds on a computer. How the brain processes these relatively simplistic and synthetic experiences may be different from how the brain handles detailed, real-world personal experiences that have personal significance to the participant.
Brown and coworkers took a different approach. They combined brain imaging with memory tests using images of events from people’s lives that were captured by wearable camera technology.
Participants wore digital cameras around their necks for three weeks. During that period, the cameras automatically captured photographs when people were active. Then brain activity was measured by functional magnetic resonance imaging while participants made memory judgments about the photographs taken by the cameras they wore.
The experimental design allowed Brown and his colleagues to figure out which brain regions are involved in recognizing personal images and which ones enable people to remember events from their lives with different degrees of detail – that is, remembering personal facts (semantic) or remembering experiences as detailed events (episodic).
WHY MEMORY RESEARCH
The ability to form and retrieve memories is essential for survival. “We flexibly draw on memories of our experiences to avoid repeating past mistakes and to plan for the future,” Brown says. “When memory fails, we may find ourselves hopelessly lost in the city streets, incorrectly planning an event, or even providing incorrect information to a jury.”
An overarching goal of Brown’s research is to understand the neural mechanisms that support human memory and goal-directed behavior and that enable avoidance of such errors. The recent study shows how memories can vary in specificity and detail.
“We show that not all autobiographical memories are created equal,” Brown says. “From prior research, we know that knowledge of non-personal facts can be spared in many cases of amnesia. One future direction is to study when memory for personal facts can rely on brain systems that are different from those associated with amnesia and diseases like Alzheimer’s. Knowing those circumstances could tell us more about what memories could be spared.”
Another question is whether some forms of autobiographical memory are more susceptible to errors than others. When are we more likely to misremember someone else’s story as our own?
“Data from our current study suggest that memory for both personal facts and experiences are resistant to being confused with other peoples’ facts or events,” Brown says, “but systematic work examining this issue is needed.”
Using cryo-electron tomography, Georgia Tech and Emory University researchers have captured images of measles viruses as they emerge from infected cells. The work advances the understanding of measles and related viruses and could suggest antiviral drug strategies likely to work across multiple members of the family that includes measles virus.
The results were published in Nature Communications.
Scientists led by Elizabeth Wright and Zunlong Ke say they can discern an internal matrix protein acting as a scaffold, with the encapsidated genetic material visible as “snakes” close to the viral membrane.
An effective vaccine is available against measles virus, which is a highly infectious pathogen. Yet scientists still don’t understand a lot about it, Ke says. Understanding the internal organization of measles virus could guide the study of related viruses, such as parainfluenza and respiratory syncytial virus (RSV), which are common causes of respiratory illnesses, as well as Nipah virus, an inspiration for the film “Contagion.”
Wright is an associate professor of pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta, director of the Robert P. Apkarian Integrated Electron Microscopy Core, and a Georgia Research Alliance Distinguished Investigator. She has an adjunct appointment in the Georgia Tech School of Biological Sciences.
Ke is a former Georgia Tech Ph.D. student of Wright’s. Ke is starting a postdoctoral position this summer at the MRC Laboratory of Molecular Biology in Cambridge, U.K.
After working with purified viruses for a long time, Wright, Ke, and colleagues decided to examine virus-infected cells. The team collaborated with Richard Plemper, who specializes in measles virus and is now at Georgia State University.
The family of viruses that includes measles, called paramyxoviruses, is difficult to handle because of their low titers, instability, and heterogeneity, Wright says. For structural studies, researchers usually concentrate and purify viruses by centrifuging them through thick solutions. But this method is tricky for measles virus, which are squishy and prone to bursting. For this reason, they are difficult to visualize.
“Instead, we grow and infect the cells directly on the grids we use for microscopy and rapidly freeze them, right at the stage when they are forming new viruses,” Ke says.
Improvements in technology have increased the resolution of imaging. Cryo-electron tomography, which is ideal for viruses that come in different shapes and sizes, uses an electron microscope to obtain a series of 2D pictures of the viruses as the sample holder is tilted to multiple angles along one axis. The images and the angular information are then used to compute the 3D volume of the virus, much like a medical CT scan, Wright says.
“We would never see this level of detail with purified virus, because the process of purification disrupts and damages the delicate virus particles,” she says. “With the whole-cell tomography approach, we can collect data on hundreds of viruses during stages of assembly and when released. This allows us to capture the full spectrum of structures along the virus assembly pathway.”
For example, the scientists can now see the organization of glycoproteins on the surface of the viral membrane. Previous work showed two glycoproteins were present on the membrane, but they were a “forest of trees,” with insufficient detail to identify each one.
In this study, the team resolved the two glycoproteins and determined that one of them, the fusion (F) protein, is organized into a well-defined lattice supported by interactions with the matrix protein. In addition, they could see “paracrystalline arrays” of the matrix protein, called M, under the membrane. The arrays had not been seen in measles virus-infected cells or individual measles virus particles before, Wright says. Under the microscope, these arrays look like Lego grid plates, from which the rest of the virus is built and ordered.
The new 3D structures also argue against a previous model of viral assembly, with ribonucleoprotein genetic material as a core and the M protein forming a coat around it.
The scientists are still figuring out what makes measles virus take a bulbous shape while RSV is more filamentous. Ke thinks the scaffold role of M is similar for related viruses; however, as the virus assembles, individual structural proteins may coordinate uniquely to produce virus particles with different shapes that better support their replication cycle.
This work was supported in part by Emory University; Children’s Healthcare of Atlanta; the Georgia Research Alliance; the Center for AIDS Research at Emory University (P30 AI050409); the James B. Pendleton Charitable Trust; public health service grants R01AI083402 and R01HD079327, R01GM114561, R21AI101775, and F32GM112517; and NSF grant 0923395.
EDITOR’S NOTE: This article is an abridged and slightly modified version of the original story by Quinn Eastman published in the Emory News Center on April 30, 2018.
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