For his latest research on motor skills, visual learning, and their effects on human physiology, School of Biological Sciences associate professor Lewis Wheaton and his team went all the way back to the Paleolithic Era to study a very retro skill: stone toolmaking.

“One of the cool things about this particular study,” Wheaton says, “is this opportunity to look at a completely novel motor task, something most people have no idea how to do, and that’s making a stone tool.”

The new research, published today in Communications Biology, attempts to fill in the gaps when it comes to the science of how we learn complex motor skills — and what may be required to relearn them. 

Wheaton says there are studies researching the behavioral changes that are involved with learning complex skills. But research is still thin on how people adapt their visuomotor skills (how vision and movements combine) to carry out a complex task. Wheaton’s current study sought to quantify and evaluate the changes and relationship in action perception processes – how we understand actions, then select, organize, and interpret what needs to be done for a particular task. 

“The overall motivation was to determine if we could see any kind of emerging relationship between the perceptual system and the motor system, as somebody is really trying to learn to do this skill,” Wheaton says. Those are important processes to understand, he adds, not just for how people attain complex motor skills learning, but what would be needed for motor relearning, as in a rehabilitation setting.

Wheaton conducted the research with graduate students Kristel Yu Tiamco Bayani and Nikhilesh Natraj, plus three researchers from Emory University’s Department of Anthropology.

Tracking the eyes to learn about learning 

The test subjects in the study watched videos of paleolithic stone toolmaking for more than 90 hours of training. The subjects’ visual gaze patterns and motor performance were checked at three different training time points: the first time they watched the video, at 50 hours of training, and at approximately 90 hours. Everybody was able to make a stone tool (with varying degrees of success) at 90 hours, but some picked up the skills at 50 hours.

Wheaton says there was a lot of information to pay attention to in the videos. “There’s a lot of physics in (making stone tools). You’re hitting a rock which is made up of all different kinds of material. There could be a fissure or fault lines, and if you hit it the wrong way it could crumble. When you’re doing it at first, you don’t know that.”

As the video training went on, the participants started to pick up cues about how to strike the rock, along with other aspects of toolmaking. “At first you’re watching from curiosity, then you’re watching with intent.”

That was the exciting part for Wheaton and his team: Being able to see the different phases of learning during the training — which they actually could see by monitoring gaze tracking, or where the subjects’ eyes landed on the video screen as they watched (see photo.)

“Part of the study was to understand the variability where they are visually focused as they get better at the task,” he says.

That’s how Wheaton’s team found there are certain parts of the skills learning that connect better to gaze, but others that connect better to the physical act of making a stone tool. “As you’re going through time, your motor abilities are changing, and at some point that allows you to watch somebody else perform the same task differently, suggesting you’re able to follow the action better, and pull more information from the video in a much clearer way.”

The study not only found a connection between gaze and motor skills learning, but that the connection evolved as the learning went on. The next step in this research, Wheaton says, should include brain imaging “heat maps” to determine where learning takes place with this process. 

That could also help Wheaton’s team apply these lessons for rehabilitation purposes.

“That’s the link between that and some of the other work we’ve done in a rehab context,” he says. “If you’re watching somebody perform a task, if you’re undergoing rehab, there are different ways you’re watching the task. You’re not always watching it the same way. Maybe it depends on how good you are, or how you’re impaired, but all those variables play a role into what you’re visually pulling out” of the rehab training.

DOI: doi.org/10.1038/s42003-021-02768-w

Atlanta is often called the “city in a forest” because of its lush canopy of trees, uncommon for a major city. In the heart of that forest sits Georgia Tech’s 400-acre campus. And within campus lies a variety of wildlife that has made Georgia Tech its home.

“I don’t think most people are aware of wildlife on campus,” said Emily Weigel, senior academic professional in the School of Biological Sciences. “They might see a feral cat here or there, but they don’t really think about all the other animals that live on campus. Georgia Tech is the animals’ home base, and they probably don’t know anything other than they were born in this area. They don’t know they’re in the middle of a city.”

Included in the biodiversity surveys of the area are squirrels, possums, raccoons, rats, and birds. Several months ago a couple of coyotes were spotted, but they were just passing through campus. At least two foxes live in the glade, a densely forested area behind the president’s residence on the north side of campus.

Ben Seleb, a Ph.D. student in quantitative biosciences, is developing an open source camera for studying the foxes and other wildlife. He and his colleagues at Tech4Wildife, a course and campus organization devoted to the conservation of wildlife, have been monitoring the foxes.

“We had some suspicions that foxes were in the glade,” Seleb said. “It’s a very secluded area with dense vegetation, so it’s a great spot for campus wildlife to hide during the day and then come out at night.”

To confirm their suspicions, they set up cameras inside the glade and left them for a couple of weeks. When they reviewed the images, they had captured two foxes on camera at the same time.

“We know there could be more, but we’ve only seen two foxes at one time. They’re difficult to tell apart, but we’re working on identifying individuals,” he said. “There are a number of other animals on campus, and the glade is where many of them live. We have seen raccoons, possums, and a couple of feral cats that travel in and out of the glade.”

The glade connects to Tech’s new EcoCommons, a lush 8-acre woodland area near the center of campus, providing a pathway for wildlife to travel into campus at night, while still giving them the cover of vegetation. Georgia Tech generally offers a handful of classes related to wildlife or ecology, but the amount of wildlife on campus is creating new research opportunities.

“I’m happy to see programs giving students opportunities that they may not have been aware of,” Seleb said.

By Frida Carrera

As one of the nation’s leading research institutions, Georgia Tech has always emphasized the pursuit of progress and service in its research endeavors. With such a strong focus on research, it is only right that many students at Tech have seized their opportunities to make an impact on the real world and solve complex problems. Taking initiative, asking the right questions, and being passionate about making a positive impact are innate characteristics that make a researcher, and Georgia Tech has in no way come short of giving rise to many exemplary researchers. The following undergraduate student researchers are serving as catalysts for innovation and development in their respective fields and are representative of Georgia Tech’s mission in developing leadership and improving the human condition. 

Prahathishree (Premi) Mohanavelu is a 5^th-year Computer Science major with a Pre-Health concentration. She conducts research with Dr. Cassie Mitchell in Biomedical Engineering on informatics-based literature mapping to personalize therapy for Chronic Myeloid Leukemia. 

“I was really looking for a way to apply the concepts I was learning in my computer science classes to the field of healthcare, and I felt this position was the perfect fit for that.” 

One of her main reasons for conducting this research was her interest in medical innovation. Premi believes the future of medicine will rely on preventative care and says her research position has also helped her with oral presentation and communication skills. Premi also serves as president of the Undergraduate Research Ambassadors and utilizes her research role and experience to teach prospective research students the ins and outs of obtaining research knowledge.

Yiyang (Diana) Wang is a 4^th-year Computer Science major conducting research with Dr. Jennifer Kim on contact tracing visualization tool design and implementation. Her research is applicable to easily contracted illnesses including COVID-19. Yiyang believes her research will help people understand the importance of contact tracing and how data collection, for contact tracing purposes, could be beneficial. Yiyang’s goal is to become a software engineer and wants to focus on improving technology for the benefit of the user. Yiyang thanks the Undergraduate Research Opportunities Program (UROP) for obtaining her position as it was a major resource for her in finding and landing her current research position. 

Milan Riddick is currently a 5^th-year Biomedical Engineering major with a minor in Health, Medicine, and Society conducting research with Dr. Jennifer Singh in the area of History, Technology, and Society on the mistrust of the COVID-19 vaccine among black citizens of Georgia. Milan has been the primary lead in her own research and has combined her passions for medical sociology and research to do what she loves. From proposing, securing funding, recruiting, and interviewing, Milan had a vision from the start and hopes to understand and improve the trust disparity between black Georgia citizens and the COVID-19 vaccine. Milan hopes her current research will aid with the trust between people and medicine as well as securing her path to graduate school.

William York is a 4^th-year Biomedical Engineering major with a concentration in Pre-Health. He is currently conducting research with Dr. Edward Botchwey on using biomaterials to immunomodulate muscular defects for tissue regeneration. He believes his research is important because it will aid in the initiative in potentially replacing stem cells with exosomes in stem cell research while retaining the same regenerative effects and creating fewer risks. William wasn’t sure about research when he first arrived at Tech, but after learning the opportunities and resources UROP had for undergraduate students, he quickly became involved. William is now currently in the Research Option program and is also an Undergraduate Research Ambassador providing guidance to students also interested in research. 

Hannah Shin is a 3^rd-year Biology major with a concentration in Physiology and is conducting research with Dr. Colin Harrison on measuring the organization of biological knowledge around experimental design utilizing a card sorting task. Hannah’s research uses its results to identify the weak areas in biology programs and make the necessary revisions to instruct students more effectively. Hannah believes her research will also aid her in future endeavors. 

 “My career goal is medical school and I believe my research will advance both my academic and career goals because it exposes me to real-world applications of data analysis and allows me to dive into the differences in knowledge organization among people of different backgrounds.” 

 Hannah is also a participant in the Research Option program and is the executive vice president of the Undergraduate Research Ambassadors. She uses her research and personal experience to help students gain confidence in pursuing research they are passionate about. 

Read more about Undergraduate Research opportunities by going to http://urop.gatech.edu. 

Cancer chemotherapy has undergone a paradigm shift in recent years with traditional treatments like broad-spectrum cytotoxic agents being complemented or replaced by drugs that target specific genes believed to drive the onset and progression of the disease.

This more personalized approach to chemotherapy became possible when genomic profiling of individual patient tumors led researchers to identify specific "cancer driver genes" that, when mutated or abnormally expressed, led to the onset and development of cancer.

Different types of cancer — like lung cancer versus breast cancer — and, to some extent, different patients diagnosed with the same cancer type — show variations in the cancer driver genes believed to be responsible for disease onset and progression. “For example, the therapeutic drug Herceptin is commonly used to treat breast cancer patients when its target gene, HER-2, is found to be over-expressed,” says John F. McDonald, professor in the School of Biological Sciences.

McDonald explains that, currently, the identification of potential targets for gene therapy relies almost exclusively on genomic analyses of tumors that identify cancer driver genes that are significantly over-expressed.

But in their latest study, McDonald and Bioinformatics Ph.D. student Zainab Arshad have found that another important class of genetic changes may be happening in places where scientists don’t normally look: the network of gene-gene interactions associated with cancer onset and progression.

“Genes and the proteins they encode do not operate in isolation from one another,” McDonald says. “Rather, they communicate with one another in a highly integrated network of interactions.”

“What I think is most remarkable about our findings is that the vast majority of changes — more than 90% — in the network of interactions accompanying cancer are not associated with genes displaying changes in their expression,” adds Arshad, co-author of the paper. “What this means is that genes playing a central role in bringing about changes in network structure associated with cancer — the ‘hub genes’ — may be important new targets for gene therapy that can go undetected by gene expression analyses.”

Their research paper “Changes in gene-gene interactions associated with cancer onset and progression are largely independent of changes in gene expression” is published in the journal iScience.

Mutations, expression — and changes in network structure

In the study, Arshad and McDonald worked with samples of brain, thyroid, breast, lung adenocarcinoma, lung squamous cell carcinoma, skin, kidney, ovarian, and acute myeloid leukemia cancers — and they noticed differences in cell network structure for each of these cancers as they progressed from early to later stages.

When early-stage cancers develop, and stayed confined to their body tissue of origin, they noted a reduction in network complexity relative to normal pre-cursor cells. Normal, healthy cells are highly differentiated, but as they transition to cancer, “[T]hey go through a process of de-differentiation to a more primitive or stem cell-like state. It’s known from developmental biology that as cells transition from early embryonic stem cells to highly specialized fully differentiated cells, network complexity increases. What we see in the transition from normal to early-stage cancers is a reversal of this process,” McDonald explains.

McDonald says as the cancers progress to advanced stages, when they can spread or metastasize to other parts of the body, “[W]e observe re-establishment of high levels of network complexity, but the genes comprising the complex networks associated with advanced cancers are quite different from those comprising the complex networks associated with the precursor normal tissues.”

“As cancers evolve in function, they are typically associated with changes in DNA structure, and/or with changes in the RNA expression of cancer driver genes. Our results indicate that there’s an important third class of changes going on — changes in gene interactions — and many of these changes are not detectable if all you’re looking for are changes in gene expression.”

DOI: https://doi.org/10.1016/j.isci.2021.103522

Acknowledgments: This research was supported by the Mark Light Integrated Cancer Research Center Student Fellowship , the Deborah Nash Endowment Fund , and the Ovarian Cancer Institute (Atlanta), where John F. McDonald serves as chief research officer. The results shown here are based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.

About Georgia Institute of Technology

The Georgia Institute of Technology, or Georgia Tech, is a top 10 public research university developing leaders who advance technology and improve the human condition. The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its nearly 40,000 students representing 50 states and 149 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning. As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society.

Black soldier fly larvae devour food waste and other organic matter and are made of 60% protein, making them an attractive sustainable food source in agriculture. But increasingly, black soldier larvae are dying before they reach livestock facilities as animal feed. 

Georgia Tech researchers, recognizing the culprit is the collective heat generated when the maggots eat in crowded conditions, have found that delivering the right amount of airflow could help solve the overheating issue. Their findings were published this month in Frontiers in Physics as part of a special issue on the “Physics of Social Interactions.”

“Black soldier fly larvae are widely used in an emerging food-recycling industry. The idea is to feed the larvae with food waste and then turn them into chicken feed,” explained first author Hungtang Ko, a Ph.D. student in the George W. Woodruff School of Mechanical Engineering.  “These larvae make a great candidate for this process because they eat just about everything.”

Each year humans waste more than one billion tons of food, or a third of all food production, and many countries are running out of options for disposing of this waste.

The larvae thrive in and around compost piles, where their larvae help break down organic material, from rotten produce to animal remains and manure. Black soldier fly larvae commonly grow to about 1,000 times their size, noted David Hu, professor in the School of Mechanical Engineering.

“It’s like going from the size of a person to the size of a big truck,” he said of the larvae’s growth from eggs to adults.

Hu has appeared on Science Friday graphically showing the voracious appetite of black soldier fly larvae, which can eat twice their body mass in food per day. But when these maggots feed while tightly packed in container bins, they generate metabolic heat that collectively can turn lethal for them.

Air Flow Matters

Ko and Hu collaborated with Daniel Goldman, Dunn Family Professor in the School of Physics, to set up the experiments. Goldman uses fluidized beds —widely used in industrial applications like oil refining ― to control properties of granular media in animal and robot locomotion studies. Fluidized beds operate by forcing a vertical flow of fluid through a collection of particulate matter; above a certain flow rate, the grains transition from a solid pile to a fluid-like arrangement, where they collide and jostle.  

The researchers placed the larvae in a container subjected to regular air flow at a consistent temperature. They then attached a leaf blower to supply air flow into the chamber, manually ramping up and down the air speed in five-minute trials.

Because of the larvae’s constant activity, the collectives’ behavior under air fluidization differs from what is observed in traditional fluidized beds: larvae were un-jammable when air flow became low. Instead, they behave like a fluid that adapted and adjusted to external forces.

“An interesting aspect of this work is that it probes a regime of ‘active matter,’ which has received less attention from physicists: Instead of 3D swarms composed of widely separated, non-colliding flying birds and insects, our `swarm’ exists in another regime, where animals are packed tightly together,” Goldman said.

In a second experiment, the team used x-ray imaging and constant air speed to see how fast larvae eat. Specifically, Ko measured the average velocity and pressure of the larvae, as well as how much food they ate under various airflow speeds.

“As you continue to increase the flow, you’ll reach a point where all the larvae are flying [through the air]. The airflow is too fast, and they won’t eat well,” he said.   

Optimal air velocity will ensure the larvae are cooled off properly and can still feed effectively. “Probing optimal flow velocity will be a good next step. Also, from an engineering perspective, we need to consider other ways that we can cool the larvae down, including using heat transfer,” he added. 

The results indicated that as larvae are agitated by rapid flows, the insects are more likely to be suspended in mid-air without contacting the food, suggesting that a moderate flow rate would be optimal for feeding dense groups of larvae.

The researchers also hope this work will enable black soldier fly larvae to be more readily available as recyclers of food waste, which totals 1.3 billion tons per year, according to the Food and Agriculture Organization of the United Nations. But just as important is the potential of these protein-rich insects to reduce the carbon effects of feeding animals. Global food production contributes more than 17 billion metric tons of human-made greenhouse gas emissions every year, according to a study published in September in Nature Food. Animal-based foods produce more than twice the emissions of plant-based food, the study found. 

“There's no sustainable protein source for the animals that we eat,” noted Ko. “The black soldier fly larvae could play a role in reducing the environmental impact of feeding these animals.”

CITATION: H. Ko, et. all, “Air-Fluidized Aggregates of Black Soldier Fly Larvae,” (Frontiers in Physics, 2021) https://doi.org/10.3389/fphy.2021.734447

As of this week, the omicron variant makes up the majority of new coronavirus cases in the U.S. Omicron is more contagious than previous variants and has caused a spike in cases across the nation, including locally.

The same prevention measures that have been put in place previously can still help slow the spread of this variant — vaccination, wearing a face covering, physical distancing, and regular surveillance testing. A well-fitting mask with good filtration is a strong defense for when you are out in public, even if you are fully vaccinated.

As the campus community looks toward winter break, Georgia Tech encourages all students, faculty, and staff to get fully vaccinated, including a booster shot. Campus vaccination clinics will resume in January; to find a vaccination site before that, visit vaccines.gov. Vaccines help reduce the risk of severe illness and hospitalization.

Anyone with Covid-19 symptoms — even mild ones — should get tested and wait for a negative result before interacting with others. Testing on campus is closed through winter break and will resume Tuesday, Jan. 4, 2022. Until then, you can find an alternate testing site.

We recommend all students, faculty, and staff plan to get tested off-campus before returning for the spring semester, and we recommend each person test again on campus upon their return. Campus testing sites will reopen at full capacity on Jan. 4th to accommodate those returning to campus.

Jenny McGuire plans to use the late Cenozoic fossil record in Africa — a span of 7.5 million years — to study the long-term relationships between animals, their traits, and how they respond to changes in their environments. The goal is to use the data to forecast future changes and help inform conservation biology decisions for the continent.

McGuire, an assistant professor with joint appointments in the School of Earth and Atmospheric Sciences and School of Biological Sciences at Georgia Tech, and her Spatial Ecology & Paleontology Lab are teaming up with an international cohort of researchers for the effort, which includes scientists from Texas A&M University, University of Cambridge, and the National Museums of Kenya. The work is jointly funded by the National Science Foundation (US NSF) and the National Environment Research Council (NERC), part of UK Research & Innovation (UKRI), a new body which works in partnership with universities, research organizations, businesses, charities and government “to create the best possible environment for research and innovation to flourish.”

McGuire says the team hopes to learn more about which functional traits vertebrates (animals with backbones) have that closely relate to shifting factors at a given location like temperature, rain and other precipitation, and their natural environment — and how those changes have occurred as environments and humans evolved.

“Community-level trait calculations correlate with specific environmental conditions,” McGuire says. “For example, in places or times when there is less precipitation, mammal communities overall will have more robust, rugged, resistant teeth. And the ankle gear ratios of mammals living in open versus more enclosed habitats reflect this condition, since animals living in more open habitats typically need to run faster.”

McGuire says Africa offers a crucial natural laboratory for these types of conservation paleobiological studies, noting a rich, well-sampled fossil record. The continent is also home to a diverse range of vertebrate ecosystems, including the most complete natural community of remaining terrestrial megafauna: large animals that include the “big five” of Africa — elephants, giraffes, hippopotamuses, rhinoceroses, and large bovines like wildebeests, antelopes, and water buffaloes.

“Critically, these megafauna are facing increasing pressures from global economic demands leading to habitat loss, as well as from changing climates,” McGuire shares.

Michelle Lawing, an associate professor in Texas A&M’s Department of Ecology and Conservation Biology, is the lead institution principal investigator for the project, and McGuire is the collaborating institution’s principal investigator. Fredrick Kyalo Manthi, co-principal investigator, is director of Antiquities, Sites, and Monuments and a senior research scientist in the Department of Earth Sciences at the National Museums of Kenya in Nairobi. Jason Head, NERC principal investigator, is a professor in the Department of Zoology at the University of Cambridge.

Responding to changing climates and environments

Related research into how communities have evolved over time, and how they’ve been impacted by terrain, animal migration, and climate change, has taken McGuire to Wyoming’s Natural Trap Cave for five of the past seven summers. There, the so-called “pit” or sinkhole cave trapped animals for millennia, leaving only their bones and other fossils remaining to tell their stories to McGuire and fellow researchers about life there more than 35,000 years ago.

“What we’re really looking at is how communities shift across the landscape,” McGuire shared in an earlier interview about the work. “So, if we have glaciers that are coming really far south in North America, how does that drive the distributions of species on the landscape and where they’re living, and whether or not there’s new communities or total remixing of communities, or if communities just shift in a uniform way?

“We’re really trying to understand how animals respond to changing climate and changing environments, so that we can get a better sense of how they’ll respond to increased warming and climate change that’s occurring today.”

Positive trait to environment relationships — and a negative one

When it comes to an example of a good trait-environment relationship involving animals, McGuire cites the role that elephants play in Africa — something mastodons also did in North America before their extinction.

“Elephants help maintain savanna habitats,” McGuire says, referring to the giants’ relationships with Africa’s grassland regions. “They control trees along the perimeters of forests, preventing them from expanding into, and taking over, savanna habitats.”

Similarly, in ancient North American ecosystems, the loss of the mammoth, along with climate change, is thought to have resulted in the loss of the mammoth steppe ecosystem, “a no-analog, widespread Arctic shrubland that went extinct as a biome (a community of plants and animals) around the time of North American megafauna extinction,” McGuire says.

The new project’s outreach efforts

The US NSF and UK NERC funding for the project also includes student outreach and mentoring for early career academics. The project’s broader impact goals include measures to support inclusivity and diversity in science, high-impact training experiences for students and postdoctoral researchers, application of the researcher’s modeling framework for applied conservation, and meaningful engagement with the public.

“This international collaborative project will also help train both Kenyan and American (and) European students, thus establishing another generation of researchers,” National Museums of Kenya’s Fredrick Kyalo Manthi says.

“We plan to pair travel and research objectives with workshops so that workshop students get to directly participate in research, and serve as co-authors on projects as appropriate,” McGuire adds.

***

Funding: NSFDEB-NERC Award #2124770; NSF CAREER Award #1945013; International Union of Biological Sciences: Conservation Paleobiology in Africa Program.

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The Georgia Institute of Technology, or Georgia Tech, is a top 10 public research university developing leaders who advance technology and improve the human condition. The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its nearly 44,000 students representing 50 states and 149 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning. As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society.

Severe and persistent disability often undermines the life-saving benefits of cancer treatment. Pain and fatigue — together with sensory, motor, and cognitive disorders — are chief among the constellation of side effects that occur with the platinum-based agents used widely in chemotherapy treatments worldwide.

A new study by Georgia Tech researchers in the lab of Timothy C. Cope has found a novel pathway for understanding why these debilitating conditions happen for cancer patients and why scientists should focus on all of the possible neural processes that deliver sensory or motor problems to a patient’s brain — including the central nervous system — and not just the “peripheral degeneration of sensory neurons” that occurs away from the center of the body.

The new findings “Neural circuit mechanisms of sensorimotor disability in cancer treatment” are published in the Proceedings of the National Academy of Sciences (PNAS) and could impact development of effective treatments that are not yet available for restoring a patient’s normal abilities to receive and process sensory input as part of post cancer treatment, in particular.

Stephen N. (Nick) Housley, a postdoctoral researcher in the School of Biological Sciences, the Integrated Cancer Research Center, and the Parker H. Petit Institute for Bioengineering and Bioscience at Georgia Tech, is the study’s lead author. Co-authors include Paul Nardelli, research scientist and Travis Rotterman, postdoctoral fellow (both of the School of Biological Sciences), along with Timothy Cope, who serves as a professor with joint appointments in the School of Biological Sciences at Georgia Tech and in the Coulter Department of Biomedical Engineering at Emory University and Georgia Tech.

Neurologic consequences

“Chemotherapy undoubtedly negatively influences the peripheral nervous system, which is often viewed as the main culprit of neurologic disorders during cancer treatment,” shares Housley. However, he says, for the nervous system to operate normally, both the peripheral and central nervous system must cooperate.

“This occurs through synaptic communication between neurons. Through an elegant series of studies, we show that those hubs of communication in the central nervous system are also vulnerable to cancer treatment’s adverse effects,” Housley shares, adding that the findings force “recognition of the numerous places throughout the nervous system that we have to treat if we ever want to fix the neurological consequences of cancer treatment — because correcting any one may not be enough to improve human function and quality of life.”

“These disabilities remain clinically unmitigated and empirically unexplained as research concentrates on peripheral degeneration of sensory neurons,” the research team explains in the study, “while understating the possible involvement of neural processes within the central nervous system. The present findings demonstrate functional defects in the fundamental properties of information processing localized within the central nervous system,” concluding that “long-lasting sensorimotor and possibly other disabilities induced by cancer treatment result from independent neural defects compounded across both peripheral and central nervous systems.”

Sensorimotor disabilities and ‘cOIN’

The research team notes that cancer survivors “rank sensorimotor disability among the most distressing, long-term consequences of chemotherapy. Disorders in gait, balance, and skilled movements are commonly assigned to chemotoxic damage of peripheral sensory neurons without consideration of the deterministic role played by the neural circuits that translate sensory information into movement,” adding that this oversight “precludes sufficient, mechanistic understanding and contributes to the absence of effective treatment for reversing chemotherapy-induced disability.”

Cope says the team resolved this omission “through the use of a combination of electrophysiology, behavior, and modeling to study the operation of a spinal sensorimotor circuit in vivo” in a rodent model of “chronic, oxaliplatin (chemotherapy)–induced neuropathy: cOIN.”

Key sequential events were studied in the encoding of “propriosensory” information (think kinesthesia: the body's ability to sense its location, movements, and actions) and its circuit translation into the synaptic potentials produced in motoneurons.

In the “cOIN” rats, the team noted multiple classes of propriosensory neurons expressed defective firing that reduced accurate sensory representation of muscle mechanical responses to stretch, adding that accuracy “degraded further in the translation of propriosensory signals into synaptic potentials as a result of defective mechanisms residing inside the spinal cord.”

Joint expression, independent defects

“These sequential, peripheral, and central defects compounded to drive the sensorimotor circuit into a functional collapse that was consequential in predicting the significant errors in propriosensory-guided movement behaviors demonstrated here in our rat model and reported for people with cOIN,” Cope and Housley report. “We conclude that sensorimotor disability induced by cancer treatment emerges from the joint expression of independent defects occurring in both peripheral and central elements of sensorimotor circuits.”

“These findings have broad impact on the scientific field and on clinical management of neurologic consequences of cancer treatment,” Housley says. “As both a clinician and scientist, I can envision the urgent need to jointly develop quantitative clinical tests that have the capacity to identify which parts of a patient nervous system are impacted by their cancer treatment.”

Housley also says that having the capacity to monitor neural function across various sites during the course of treatment “will provide a biomarker on which we can optimize treatment — e.g. maximize anti-neoplastic effects while minimizing the adverse effects,” adding that, as we move into the next generation cancer treatments, “clinical tests that can objectively monitor specific aspects of the nervous system will be exceptionally important to test for the presence off-target effect.”

***

FUNDING: This work is supported by NIH Grants R01CA221363 and R01HD090642 and the Northside Hospital Foundation, Inc.

DOI: doi.org/10.1073/pnas.2100428118

ACKNOWLEDGMENTS: The researchers thank Marc Binder (Department of Physiology & Biophysics at University of Washington) and Todd Streelman (School of Biological Sciences at Georgia Tech) for providing useful discussions and comments on a preliminary version of the manuscript. Lead author Housley also serves as chief scientific officer for Motus Nova, a healthcare robotics and technology company.

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The Georgia Institute of Technology, or Georgia Tech, is a top 10 public research university developing leaders who advance technology and improve the human condition. The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its nearly 44,000 students representing 50 states and 149 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning. As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society.

Because humans and animals breathe and metabolize oxygen, they generate a variety of reactive oxygen species (ROS), or cell-damaging oxidants, as byproducts. Our bodies usually make enough antioxidants to counter that damage, but when that balance starts to favor oxidants, they can attack important biomolecules like proteins, nucleic acids, and lipids. That can lead to cancer, neurodegenerative disorders, and cardiovascular diseases.

Fortunately, our bodies evolved to produce antioxidant enzymes such as Cu/Zn (copper/zinc) superoxide dismutase, or SOD1, which detoxifies certain harmful oxidants. In a weird twist, SOD1 is the only antioxidant enzyme that can take on one specific oxidant, superoxide, only to produce another ROS: hydrogen peroxide.

A team of Georgia Tech researchers have published a study that found an even stranger twist to this oxidant-antioxidant tale: SOD1 (good for cells) produces hydrogen peroxide (bad for cells) which stimulates the production of another important cellular antioxidant known as NADPH (also good for cells; more on this in a moment.)

“Yes, you heard that right,” says Amit Reddi, associate professor in the School of Chemistry and Biochemistry. “SOD1, an antioxidant enzyme, produces an oxidant, hydrogen peroxide, which in turn stimulates the production of another (good) antioxidant.”

Reddi is a co-author of this research along with Matthew Torres, associate professor in the School of Biological Sciences; Claudia Montllor-Albalate, former Reddi Lab member who received her Ph.D. in 2020 from the School of Chemistry and Biochemistry; Hyojung Kim, School of Chemistry and Biochemistry Ph.D. candidate; Annalise Thompson, a third-year graduate student in Reddi’s lab; and Alex Jonke, research scientist with the School of Biological Sciences. 

Their study, “SOD1 Integrates Oxygen Availability to Redox Regulate NADPH Production and the Thiol Redoxome” is published in the Proceedings of the Natural Academy of Sciences (PNAS).

The NADPH/GAPDH connection

NADPH (nicotinamide adenine dinucleotide phosphate) is an important metabolite that is produced in cells. It provides a source of electrons that can act as an antioxidant and for the biosynthesis of numerous biomolecules, including fatty acids, amino acids, nucleotides, and cholesterol. 

“NADPH is not only used as an antioxidant, but also to build new biomolecules to sustain cell proliferation,” Reddi says. “How do cells know to make enough NADPH to support aerobic life?  We discovered that SOD1 senses oxygen availability via superoxide, and then converts this to hydrogen peroxide, which in turn inactivates an enzyme responsible for the breakdown of glucose, glyceraldehyde phosphate dehydrogenase (GAPDH).” That inactivation causes the build-up of metabolites that are re-routed to a pathway that synthesizes NADPH.

The story behind the SOD1 revelation

The PNAS research study began with a casual conversation in 2014 between Reddi and Torres at the former café in the Parker H. Petit Institute for Bioengineering and Biosciences (IBB). 

“Given the very collaborative and collegial nature of faculty across the College of Sciences, and the Institute as a whole, it was easy to grab a coffee and discuss these ideas,” Reddi says. Work in the Reddi lab includes potential signaling roles for SOD1 and the hydrogen peroxide it produces; but understanding the extent to which these factors regulate signaling required a systems-level understanding of how widespread targets of SOD1 are in a cell. 

Torres focuses on mass spectrometry-based proteomics (the study of all proteins produced and modified by an organism or system) to probe cell-wide signaling networks, so it seemed to Reddi like a perfect fit.

Then, Reddi says, Montllor-Albalate made the discovery that SOD1-derived hydrogen peroxide can regulate NADPH production and adaptation to aerobic life.  Meanwhile, Kim, a joint student of the Reddi and Torres labs, drove the work to identify proteome-wide targets of SOD1-derived hydrogen peroxide. 

The conversation in IBB led to a 2016 grant from the National Institutes of Health to study the topic further. The resulting paper “we feel will make a strong impact in the field of redox biology and signaling,” Reddi adds. 

SOD1’s potential in future cancer therapy

SOD1 is often thought of as an appealing anti-cancer therapeutic because of its ability to scavenge superoxides. The theory is that if SOD1 is inactivated, cancer cells will be at a disadvantage. 

Reddi says his team’s results “suggest this very simple approach may need to be reconsidered, because the hydrogen peroxide that is produced by SOD1 plays broader roles in metabolism — and regulates many other enzymes and pathways. For instance, many cancer cells are addicted to glucose (sugars) and have an increased reliance on it for energy and metabolism, with GAPDH being a key enzyme in the process. Our findings that SOD1-derived hydrogen peroxide inactivates GAPDH would suggest that inhibiting SOD1 in certain cancers could actually result in elevated GAPDH activity, and increased metabolism of glucose, which may be detrimental in fighting cancer.”

Torres and Reddi are continuing their collaboration to investigate other aspects of SOD1 and hydrogen peroxide signaling in cancer metabolism and its implications for disease progression.

doi.org/10.1073/pnas.2023328119

This work was supported by GM118744 to Reddi and Torres, and Blanchard Fellowship to Reddi. 

James Stringfellow, an employment specialist with a history of helping Atlanta-based veterans and entertainment industry staff in the workforce, has been named the first career educator for the College of Sciences.

“I am thrilled to have James join the Georgia Tech Career Center,” says Laura Garcia, director of Career Education Programs. “I hope everyone gives him a warm welcome to the Georgia Tech community.” 

Stringfellow, who began his duties on January 4, leads the following initiatives:

• Assisting students with career mapping, co-op and internships, and workforce preparedness.
• Supporting College of Sciences programs by facilitating career education events.
• Supporting College instructors with employer updates and industry trends.
• Developing employer partnerships to cultivate employment opportunities. 
• Assisting the Career Center team in meeting its community goals.

Stringfellow will be available for remote meetings from 8 a.m. to 5 p.m. on Mondays and Tuesdays. He will work out of Room 2-90 in the Boggs Building from 8 a.m. to 5 p.m. Wednesdays and Thursdays, and at the Georgia Tech Career Center (located on the first floor of the Bill Moore Student Success Center) from 8 p.m. to 5 p.m. on Fridays.

Stringfellow previously worked for the Veterans Empowerment Organization (VEO) as their employment specialist responsible for assisting veterans with re-entry into the civilian workforce. Prior to the VEO, he served as an award-winning career services manager at SAE Institute where he oversaw employer outreach and graduate employment for audio, film, and entertainment business programs. Stringfellow also worked for DeVry University in both career services and admissions in support of its College of Health Sciences.  

Stringfellow earned a bachelor’s degree in Marketing from Tuskegee University, and received his MBA in International Business from Keller Graduate School of Management at DeVry. A member of Phi Beta Sigma Fraternity, Stringfellow shares that he stays connected to the entertainment industry by coaching creatives on how to protect their musical brand, speaking at related conferences, and serving as a disc jockey at various events throughout Atlanta.

“I am thrilled to have James join the College of Sciences,” shares Cameron Tyson, assistant dean for Academic Programs in the College of Sciences. 

Tyson and Garcia also extend a special thanks to the new role’s search committee for their “hard work and finding a great addition to our team.” Committee members included:

• Alonzo Whyte (search chair), academic professional, Undergraduate Neuroscience Program
• Andrew Newman, professor and undergraduate coordinator, School of Earth and Atmospheric Sciences
• Enid Steinbart, principal academic professional and director of Undergraduate Advising and Assessment, School of Mathematics
• Mariah Liggins, advisor for Pre-Health, Pre-Graduate and Pre-Professional Advising
• Mackenzie Pierce, undergraduate student, School of Psychology