Microorganisms are highly abundant in the surface ocean, reaching densities exceeding a billion organisms per liter. Collectively responsible for roughly half of global carbon fixation, diverse groups of microbes coexist while relying on limited nutrients even as some microbes depend on energy from the sun to grow via photosynthesis. 

Precisely because microbes compete for scarce nutrients, how such a vast diversity of ocean microbes coexist has long puzzled scientists. A collaborative group of researchers from 13 institutions aimed to shed light on the subject as part of new work published today in Nature Ecology and Evolution led by Joshua Weitz, Professor and Tom and Marie Patton Chair in the School of Biological Sciences at Georgia Tech.

“The pressing matter of survival for many microorganisms at the surface is acquiring enough nitrogen,” explains Daniel Muratore, a doctoral candidate in Quantitative Biosciences at Georgia Tech and one of three co-first authors of the study. “Since microbes need to acquire nitrogen to function, we might imagine that the particular microbial type that is best at acquiring nitrogen will ultimately win – because it'll be able to grow faster than everything else. And yet that's not the case.”

By integrating data on the timing of metabolic processes of different microbes in the surface ocean throughout the 24-hour light cycle – from the transcription of genes for metabolic proteins to the synthesis of macromolecules like lipids – the researchers discovered that the coexistence of diverse microbes is shaped by the timing of uptake.

“What we saw when we let the data speak for itself was that nitrogen uptake and assimilation had some of the most distributed timing, where different microbes are doing similar metabolic processes at different times of day,” Muratore explains. While genes associated with the uptake of a scarcer resource like nitrogen were transcribed at different times by different organisms, microbes tended to transcribe genes related to carbon metabolism and photosynthesis during daytime hours while the sun was shining.

With staggered nitrogen uptake, Muratore points out that “instead of having to compete with the whole field, [microbes] only have to compete with the organisms that share that specific shift with them. Perhaps that's one way that the competition is alleviated and can facilitate all of these diverse microbes being able to live off of the same nutrient source.”

A deep dive into microbial metabolism

The study began in 2015, when scientists across disciplines in the Simons Foundation’s Simons Collaboration on Ocean Processes and Ecology (SCOPE) collected different types of data looking at microbes in the surface of the North Pacific Subtropical Gyre, the Earth’s largest stretch of contiguous ocean. “[We were interested in] understanding how that fluctuation of photosynthesis during the day and the absence thereof at night propagates through the microbial community [in the ocean],” explains Angela Boysen, co-first author on the study who conducted this research while a doctoral student at the University of Washington and is now a postdoctoral researcher at the University of Chicago. “Fluctuations in energy input influence how the ecosystem overall functions, how much carbon is stored, where the carbon moves around, and how organisms might interact with each other.”

Data on metabolic processes were collected simultaneously from the same body of water every four hours, giving researchers an unprecedented look at how metabolic activity differs among these microbes throughout the 24-hour day-night cycle. “Collecting all these different sample types – genes, metabolites, lipids, chemical, etc. – at the same time is really a first way to look at the whole ecosystem all at once from all these different perspectives,” Matthew Harke, a co-first author of the study and a research scientist at the Gloucester Marine Genomics Institute, shares. “That's something that has rarely, if at all, been done.”

The research cruise ultimately yielded data on over 65,000 unique genetic transcripts, metabolic markers, and macromolecules over time in multiple types of organisms, making the integration and interpretation of the data a big challenge. To make the data more interpretable, authors turned to machine learning methods, which work to cluster together data with similar patterns over time. 

The emergent data clusters revealed that most of the activity occurred at four time points: dusk (6 p.m.), night (2 a.m.), morning (6 a.m.), afternoon (between 10 a.m. and 2 p.m.). While these times were important for the many types of microbes studied, the key metabolic activities at each time differed. For instance, photosynthesizing microbes expressed genes coding for proteins important in nitrogen uptake pathways the most at dusk, while organisms that rely on external organic matter for energy expressed these genes most in the morning. Transcription of genes associated with iron uptake, another scarce resource in the open ocean, also took place at different times across species.

By uncovering new evidence that staggering resource uptake is potentially critical for the co-existence of diverse marine microbes, Harke highlights that “this paper really makes us re-think our perception of what it’s like to be a microbe in the ocean.” The ocean is vast, and the researchers are hoping to examine how widely their findings hold.

“In the North Pacific Subtropical Gyre, we see fairly stable waters, we have day and night cycles that are fairly stable across the seasons,” Harke explains. “What does it look like in an area of the world where that’s not stable? Do these types of things repeat themselves in coastal regions, or at other scales that we might want to look at, or other parts of the world with different dynamics that might be influencing physiology? Those are the big questions that come out of this.”

DOI: https://doi.org/10.1038/s41559-021-01606-w

This work was supported by grants from the Simons Foundation as part of the SCOPE collaboration (Simons Foundation grants 329108, 721244, 721223, 721252, 721256, 724220, 723787, 721229, 721225, and 721231), an NSF Graduate Research Fellowship, the Postdoctoral Scholarship Program at Woods Hole Oceanographic Institution & U.S. Geological Survey, and the Simons Collaboration on Computational Biogeochemical Modeling of Marine Ecosystems (Simons Foundation grant 549894).

The American Society for Pharmacology and Experimental Therapeutics (ASPET) has announced that a 2022 Molecular Pharmacology Early Career Award will be presented to Dr. Matthew Torres, faculty member in the School of Biological Sciences, in recognition of his scholarly achievements as a junior investigator in the field of molecular pharmacology.

Dr. Torres is receiving this award in recognition of his innovative research that combines genetics, mass spectrometry, and cutting-edge bioinformatics to understand how post-translational modifications impact protein function and cell physiology, and also in recognition of his strong commitment to teaching, mentoring and service. Dr. Torres is currently an Associate Professor in the School. He received his PhD in biochemistry and completed his postdoctoral training at the University of North Carolina at Chapel Hill.

The primary focus of Dr. Torres’s lab is to combine yeast genetics, mass spectrometry (MS) and bioinformatics to understand how post-translational modifications (PTMs) impact protein structure, function and cell behavior. His group studies how PTMs regulate G protein signaling pathways, with a current emphasis on the G protein gamma subunit. His lab also developed SAPH-ire (“Systematic Analysis of PTM Hotspots”), a bioinformatics tool that employs machine learning to prioritize PTMs important for protein function and provide recommendations for experimental analysis. Dr. Torres has been a member of ASPET since 2017.

The award will be presented by the Division for Molecular Pharmacology at the ASPET Annual Meeting in Philadelphia on Monday, April 4, 2022 where Dr. Torres will deliver a lecture on his research titled "From m/z to Gαβγ: Accessing the Collective Wisdom in Proteomics to Reveal Posttranslational Governors of G protein Signaling".

The talk will focus on the development of protein bioinformatic and computational tools that revealed how Gγ subunits - through phosphorylation of their intrinsically disordered N-termini - can serve as governors of Gβγ signaling.

Story adapted from:

2022 ASPET Award Winners

Yogasudha Veturi, Ph.D.
Department of Genetics
Perelman School of Medicine
University of Pennsylvania

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ABSTRACT
Plasma lipids are heritable risk factors forheart disease,but genes linked to lipids may also have ties to many other diseases including psoriasis, multiple sclerosis, Alzheimer’s disease, and chronic inflammation,a phenomenon known as pleiotropy. Our study hypothesis was simple: plasma lipids are likely to have genetic overlaps with a broad range of complex human diseases. We asked a series of questions to address this hypothesis: Firstly, can integrating plasma lipids with gene expression levels in lipid-relevant tissues identify novel lipid-associated genes that robustly replicate in the same tissue across multiple cohorts? Secondly, how many of these lipid-associated genes are also functionally linked to diseases in Electronic Health Records (EHR)? And thirdly, can we use the set of lipid-associated functional variants to determine which diseases could have causal pathways withlipids?We developed a comprehensive study to investigate these questions using an extensive ensemble of computational methods. Our overall framework can (1) visualize the complete landscape of pleiotropy between lipids and diseasesin the EHR, (2) identify diseases for which lipids could be modifiable exposures and (3) prioritize genes for functional validation in molecular/biological assays. We detected 67 novel and 954 previously reported lipid-associated genes. 80 of these were robustly linked to 73 disease codes in the EHR, including nasal polyp, malignant neoplasms of skin, loss of pelvic support in females, and asthma with notably opposite direction of gene effects for lipids and multiple sclerosison chromosome 6. Other novel findings include putative causal pathways between lipidsand gout, skin and nail infectionsas well as elevated blood sodium levels. We present a phenome-wide overview of the complex interplay between lipids, genetics, gene expression, and diseases in the EHR along with interactive visualizations and a tool to computationally assess gene-level functional associations. We have made all our summary statistics publicly available. The detected genes arecandidatesfor functional validation and drug repurposing.

SPEAKER BIO
Yogasudha Veturi is a postdoctoral scholar in the Department of Genetics at the University of Pennsylvania, mentored by Dr. Marylyn Ritchie. She holds a master’s degree in statistics from North Carolina State University and a master’s (thesis) degree in plant quantitative genetics from the University of Delaware under the mentorship of Dr. Randall Wisser. She completed her Ph.D. studies under the mentorship of Dr. Gustavo de los Campos at the University of Alabama at Birmingham and Michigan State University, where she developed statistical methods to understand the extent of genetic heterogeneity between ethnic groups and sexes for complex human traits. Her current research interests include integration of multi-omic and environmental data with electronic health records to understand the genetic etiology of complex human traits and diseases and pleiotropic relationships among traits and diseases across the “phenome”.

Event Details

Andrew Fink, Ph.D. and Carl Schoonover, Ph.D.
Department of Neuroscience
Columbia University / Howard Hughes Medical Institute

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ABSTRACT
We have discovered that in the rodent primary olfactory cortex (piriform) the pattern of neural activity evoked by a smell changes with the passage of time. These changes, which unfold absent a task or learning paradigm, accumulate to such an extent that after just a few weeks odor responses bear little resemblance to their original form. The piriform has been traditionally hypothesized to establish the identity of odorants. Our observations have forced us to radically reconsider the role of this vast brain region in olfactory perception. We propose that the piriform operates instead as a flexible learning system, a ‘scratch pad’ that continually learns and continually overwrites itself. This poses the problem of how transient memory traces can subsequently be stored over long timescales.

These results also raise the question of what the piriform learns. We have designed a behavioral assay that provides a sensitive readout of whether mice expect a given sensory event. Using this assay we have demonstrated that mice learn the identity, order and precise timing of elements in a sequence of neutral odorants, A-->B, without reward or punishment. Simultaneous recordings in naïve piriform show strong and distinct responses to both A and B. These diminish with experience in a manner that tracks these expectations: predictable cues, such as B in the A-->B sequence, evoke hardly any response in experienced animals. This does not reflect simple adaptation. When B is presented alone, it elicits robust activation. When B is omitted, and A is presented alone, piriform exhibits vigorous activity at the precise moment when the animal, expecting odor B, encounters nothing. Thus, when the external world conforms to expectation, piriform is relatively quiescent, but any departure from the expected results in vigorous activation. We hypothesize that the piriform learns to implement a comparator that reports the difference between the world as it expects it and the world as it is. The biological learning mechanisms that generate this predictive activity, a feature more commonly encountered in higher order cortices, can be readily studied and probed in a circuit only two synapses from the sensory periphery.

SPEAKER BIOS
We are postdoctoral fellows in Richard Axel’s laboratory at Columbia University, where we carry out a shared research program. We seek to understand how organisms learn continuously while also storing stable memories over their lifetimes. The rodent olfactory system, an easily accessible, well-defined circuit whose input can be precisely controlled, presents a relatively simple and tractable model to address these basic open problems. We have established methods for long-term observation of neurophysiological activity in the rodent primary olfactory cortex (piriform), and developed naturalistic ethological behavioral paradigms to probe continuous learning.

As graduate students, Carl Schoonover (BA Philosophy, Harvard College) studied the thalamocortical projection to primary somatosensory cortex under the supervision of Dr. Randy Bruno, and Andrew Fink (BA Physics, Carleton College) studied spinal presynaptic inhibition under the supervision of Dr. Thomas Jessell. 

Host: Dr. Tim Cope

Event Details

Bradley Colquitt, Ph.D.
School of Medicine
University of California San Francisco
Howard Hughes Medical Institute

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ABSTRACT
From elaborate avian courtship dance and whale song to intricate spider webs and cephalopod camouflage, nature abounds with complex behaviors generated by brains with diverse architectures and evolutionary histories. Understanding the organizational principles and innovations that connect brain and behavior across species is a fundamental challenge in neurobiology and one that has tremendous import for deciphering how nervous systems function and evolve. Courtship song in songbirds is a complex learned motor behavior and provides an ideal system in which to study the links connecting the development and evolution of cells, circuits, and behavior. In this talk, I will first present published work in which I used cellular transcriptomics to characterize the molecular identities of cells in the birdsong motor pathway and found that avian song control circuits and the mammalian neocortex contain overlapping cellular types yet reside in non-homologous brain structures. Second, I will discuss ongoing work that combines neural circuit-wide gene expression profiling with quantitative birdsong analysis to characterize the molecular pathways that contribute to motor stability. Combined, this work provides the foundation for future research that integrates cell-resolved molecular profiling, comparative neurobiology, and behavioral analysis to understand the development and evolution of birdsong and its neural circuitry, providing a window into the shared principles underlying vertebrate neural circuit organization and the cellular innovations that support behavioral evolution.

Event Details

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.

***

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.

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

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 SciencesClaudia 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. 

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.

Farzaneh Najafi, Ph.D.
Allen Institute

BlueJeans Livestream

ABSTRACT

Predictive coding is a theory of brain function that assumes the brain contains an internal model of the world, which constantly generates predictions about our environment, and updates the predictions if they deviate from the actual external inputs. It is suggested that predictive processing in the brain is impaired in neurological disorders such as schizophrenia and autism, underlying symptoms such as hallucinations and social disconnection. Treating these disorders requires understanding the neural mechanisms that generate and update prediction signals in the healthy brain. My research vision is to shed light on the brain-wide circuits and computations that underlie predictive processing.

I will start my talk by presenting data from my previous and ongoing research that demonstrate the representation of predictive signals in cortical and cerebellar circuits in behaving mice. Then I will describe the gap in our knowledge about how the cerebellum and cortex may interact to support predictive behavior. I will briefly present my future research plans that allow investigating these unknown questions, and help us gain insight into the cortico-cerebellar circuitries that underlie predictive processing.

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