Nolan English
School of Biological Sciences
Advisor: Dr. Matthew Torres (School of Biological Sciences)
Committee Members:
Dr. Melissa Kemp, School of Biomedical Engineering; Georgia Institute of Technology
Dr. Raquel Lieberman, School of Chemistry and Biochemistry; Georgia Institute of Technology
Dr. Peng Qiu, School of Biomedical Engineering; Georgia Institute of Technology
Dr. Christopher Rozell, School of Electrical and Computer Engineering; Georgia Institute of Technology
Abstract:
Post-translational modifications (PTMs) provide an extensible framework for regulation of protein behavior beyond the diversity represented within the genome alone. While the rate of identification of PTMs has rapidly increased in recent years, our knowledge of PTM functionality remains limited. Fewer than 4% of all eukaryotic PTMs are reported to have biological despite their ubiquity across the proteome. This percentage continues to decrease as the pace of identification of PTMs surpasses the rate that PTMs are experimentally researched. To bridge the gap between identification and interpretation we have developed SAPH-ire, Structural Analysis of PTM Hotspots, a machine learning based tool for prioritizing PTMs for experimental study by functional potential. In this thesis, I aim to expand SAPH-ire’s functionality to predict potential function and improve its performance in ranking PTMs by functional potential. Here I will first discuss some challenges facing computational PTM research from an informatics perspective. I will then discuss the creation of new resources to address these challenges in four objectives. First, the creation of a new data resource that captures experimental data from mass spectrometry experiments designed to focus on PTMs. Second, the renovation of the SAPH-ire machine learning model to improve model performance and predictive recall. Third, the generation of a new model capable of discerning function from functional potential and structural features. Fourth, the development of a visual interface for SAPH-ire and the data resource that enhance one’s ability to understand the model’s results and drives further study.
Post-translational modifications (PTMs) provide an extensible framework for regulation of protein behavior beyond the diversity represented within the genome alone. While the rate of identification of PTMs has rapidly increased in recent years, our knowledge of PTM functionality remains limited. Fewer than 4% of all eukaryotic PTMs are reported to have biological despite their ubiquity across the proteome. This percentage continues to decrease as the pace of identification of PTMs surpasses the rate that PTMs are experimentally researched. To bridge the gap between identification and interpretation we have developed SAPH-ire, Structural Analysis of PTM Hotspots, a machine learning based tool for prioritizing PTMs for experimental study by functional potential. In this thesis, I aim to expand SAPH-ire’s functionality to predict potential function and improve its performance in ranking PTMs by functional potential. Here I will first discuss some challenges facing computational PTM research from an informatics perspective. I will then discuss the creation of new resources to address these challenges in four objectives. First, the creation of a new data resource that captures experimental data from mass spectrometry experiments designed to focus on PTMs. Second, the renovation of the SAPH-ire machine learning model to improve model performance and predictive recall. Third, the generation of a new model capable of discerning function from functional potential and structural features. Fourth, the development of a visual interface for SAPH-ire and the data resource that enhance one’s ability to understand the model’s results and drives further study.
Post-translational modifications (PTMs) provide an extensible framework for regulation of protein behavior beyond the diversity represented within the genome alone. While the rate of identification of PTMs has rapidly increased in recent years, our knowledge of PTM functionality remains limited. Fewer than 4% of all eukaryotic PTMs are reported to have biological despite their ubiquity across the proteome. This percentage continues to decrease as the pace of identification of PTMs surpasses the rate that PTMs are experimentally researched. To bridge the gap between identification and interpretation we have developed SAPH-ire, Structural Analysis of PTM Hotspots, a machine learning based tool for prioritizing PTMs for experimental study by functional potential. In this thesis, I aim to expand SAPH-ire’s functionality to predict potential function and improve its performance in ranking PTMs by functional potential. Here I will first discuss some challenges facing computational PTM research from an informatics perspective. I will then discuss the creation of new resources to address these challenges in four objectives. First, the creation of a new data resource that captures experimental data from mass spectrometry experiments designed to focus on PTMs. Second, the renovation of the SAPH-ire machine learning model to improve model performance and predictive recall. Third, the generation of a new model capable of discerning function from functional potential and structural features. Fourth, the development of a visual interface for SAPH-ire and the data resource that enhance one’s ability to understand the model’s results and drives further study.
Event Details
A Frontiers in Science Lecture by Mindy-Millard Stafford, School of Biological Sciences
Recent work from the lab of Mindy Millard-Stafford brings attention to the cognitive effects of dehydration. The findings have garnered immense media attention, from Newsweek and National Public to Men’s Health Magazine. Millard-Stafford discusses her Georgia Tech research leading up to this widely noticed work.
She will discuss: Why is water essential? How much do we need? Is water the most hydrating beverage? Can you drink too much water? And based on one media headline -- Does dehydration make you dumber?
She will reflect on the unexpected media blitz: how it happened and what lessons we might take away from this experience.
Light refreshments will be served after the lecture.
About The Speaker
A member of the Georgia Tech faculty for more than three decades, Mindy Millard-Stafford is a professor in the School of Biological Sciences, where she directs the Exercise Physiology Laboratory.
She is past president of the American College of Sports Medicine and member of the National Academy of Kinesiology.
The goals of her research are to seek nutritional and exercise interventions that can improve human health, well-being, and performance. Her lab is particularly focused on the importance of hydration to delay fatigue and maintain safety during exercise, especially in conditions of heat stress.
About The Frontiers in Science Lecture Series
Lectures in this series are intended to inform, engage, and inspire students, faculty, staff, and the public on developments, breakthroughs, and topics of general interest in the sciences and mathematics. Lecturers tailor their talks for nonexpert audiences.
Event Details
College of Sciences faculty, staff, and students are invited to join Provost Rafael L. Bras and Search Committee Chair Pinar Keskinocak, for a town hall to learn about the dean search process and timeline, and to provide feedback on the characteristics of the ideal candidate.
The international search for the new dean for the College of Sciences will be chaired by Pinar Keskinocak, William W. George Chair, H. Milton Stewart School of Industrial and Systems Engineering; College of Engineering ADVANCE Professor; and Director, Center for Health and Humanitarian Systems. The individual selected by this search committee will also hold the Betsy Middleton and John Clark Sutherland Chair.
Event Details
Episode 2 of ScienceMatters' Season 1 stars Jenny McGuire. The assistant professor in the School of Earth and Atmospheric Sciences and the School of Biological Sciences has a tough commute to her summer research site: An 80-foot drop into Wyoming’s deep, dark Natural Trap Cave. There she collects fossils that she hopes will yield clues about the impact of climate change on animal and human populations.
Follow her journey at sciencematters.gatech.edu.
Enter to win a prize by answering the episode's question:
What small four-legged animals mentioned in Episode 2 help Jenny McGuire collect bones from Natural Trap Cave?
Submit your entry by noon on Friday, Aug. 31, at sciencematters.gatech.edu. Answer and winner will be announced on Monday, Sept. 3.
Congratulations to Vineeth Aljapur, winner of Episode 1 quiz. Aljapur is a first-year student in the Georgia Tech Bioinformatics Graduate Program.
Episode 3 of ScienceMatters' Season 1 stars M.G. Finn. Listen to the podcast and read the transcript here!
Leishmaniasis is a scary parasitic disease; it can rot flesh. Formerly contained in countries near the equator, it has arrived in North America. School of Chemistry and Biochemistry Professor and Chair M.G. Finn explains why it’s so tough to fight this disease. His collaboration with Brazilian researcher Alexandre Marques has raised hopes for a possible vaccine.
Follow the the researchers' journey at sciencematters.gatech.edu.
Enter to win a prize by answering the episode's question:
What sugar molecule mentioned in Episode 3 is the main reason surgeons can’t transplant organs from animals into humans?
Submit your entry by noon on Friday, Sept. 7, at sciencematters.gatech.edu. Answer and winner will be announced on Monday, Sept. 10.
Results of Episode 2 Quiz
Q: What small four-legged animals mentioned in Episode 2 help Jenny McGuire collect bones from Natural Trap Cave?
A: Wood rats, pack rats, or rats
The winner is Pedro Marquez Zacarias. He was listening to ScienceMatters while doing routine data analysis for his research.
A third-year Ph.D. student in the Georgia Tech Quantitative Biosciences Graduate Program, Marquez Zacarias aims to add to the understanding of how biological complexity evolved, particularly multicellularity.
Marquez Zacarias comes from a small town in rural México, an indigenous community called Urapicho, in the state of Michoacán.
They may look a little like space capsules, but nuclear magnetic resonance spectrometers stay planted on the floor and use potent magnetism to explore opaque constellations of molecules.
Three Atlanta area universities jointly launched a nuclear magnetic resonance collaboration called the Atlanta NMR Consortium to optimize the use of this technology that provides insights into relevant chemical samples containing so many compounds that they can otherwise easily elude adequate characterization. The consortium has been operating since July 2018.
Crab pee
Take, for example, crab urine. It’s packed with hundreds to thousands of varying metabolites, and researchers at the Georgia Institute of Technology wanted to nail down one or two of them that triggered a widespread crab behavior. Without access to NMR they may not have found them at all even after an extensive search.
The spectrometer pulled the right two needles out of the haystack, so the researchers could test them on the crabs and confirm that they were initiating the behavior.
Emory University, Georgia State University and Georgia Tech already have NMR technology, but the Atlanta NMR Consortium will enable them to fully exploit it while cost-effectively staying on top of upgrades.
“NMR continues to grow and develop because of technological advances,” said David Lynn, a chemistry professor at Emory University.
That means buying new machines every so often, and one new NMR spectrometer can run into the millions; annual maintenance for one machine can cost tens of thousands of dollars. Thus, reducing costs and maximizing usage makes good sense.
Medicine, geochemistry
The human body, sea-side estuaries, and rock strata present huge collections of compounds. NMR takes inventory of complex samples from such sources via the nuclei of atoms in the molecules.
A nucleus has a spin, which makes it magnetic, and NMR spectrometry’s own powerful magnetism detects spins and pinpoints nuclei to feel out whole molecules. These can be large or small, from mineral compounds with three or four component atoms to protein polymers with tens of thousands of parts.
Researchers in medicine, biochemistry, ecology, geology, food science – the possible list is exhaustive -- turn to NMR to untangle their particular molecular jungles. The consortium wants to leverage that diversity.
“As we go in different directions, we will benefit from a cohesive community of people who know how to use NMR for a wide range of problems,” said Anant Paravastu, an associate professor in Georgia Tech’s School of Chemical and Biomolecular Engineering.
“The most important goal for us is the sharing of our expertise,” said Markus Germann, a professor of chemistry at Georgia State.
Consortium members will benefit the most from the pooled NMR resources, but non-partners can also book access. Read more about the Atlanta NMR Consortium here on Georgia Tech’s College of Sciences website
Mention “peat moss,” and many people will conjure up the curly brown plant material that gardeners use. “Oh, the thing you get at Home Depot” – is a common reaction Joel Kostka receives when he mentions that he studies peat moss. His response: “Peat moss is a really cool plant that’s important to the global carbon cycle.”
Joel Kostka is a professor in the School of Biological Sciences and the School of Earth and Atmospheric Sciences at Georgia Tech. The National Science Foundation has just awarded him and three co-principal investigators a $1.15 million, three-year grant to study the microbes in peat moss. The goal is to understand the microbiome’s role in nutrient uptake and the methane dynamics of wetlands and the impact of climate change on these activities.
Kostka’s collaborators are Jennifer Glass, an assistant professor in the Georgia Tech School of Earth and Atmospheric Sciences; Xavier Mayali, a research scientist at Lawrence Livermore National Laboratory; and David Weston, a staff scientist at Oak Ridge National Laboratory.
“It has been shown that microbes that live with peat moss help them to grow better by aiding their uptake of carbon and major nutrients such as nitrogen,” Kostka says. “This project will explore which microbes help to keep peat moss plants healthy, how plants and microbes interact, and how these relationships will be affected by climate change?”
Peat moss, also called Sphagnum, carpets the surface of peatlands. This type of wetland locks up huge amounts of carbon in the form of thick, peat soil deposits. When peat is broken down by microbes, greenhouse gases – methane and carbon dioxide – are produced. Methane is of particular interest, because when released to the atmosphere, it has a warming potential that is 21 times that of carbon dioxide.
Scientists hypothesize that environmental warming could cause peatlands to release a lot more methane, which in turn would accelerate climate change.
“Our project is fundamental science. We’re trying to figure out how the microbes help the plants grow better.”
Lots of evidence suggest that peatlands will produce more methane as the environment warms up. “Methanogens [methane-producing bacteria] don’t like the cold,” Kostka says. “The warmer it gets, the better they are in producing methane.”
Methane in peatlands bubbles up to the peat moss layer. Methane-consuming microbes in peat moss eat some of the gas released. In effect, microbes in peat moss comprise a biofilter that reduces the amount of methane reaching the atmosphere.
However, “we hypothesize that the methane-eating microbes in peat moss may crash as the climate gets warmer,” Kostka says. That sets up a double-whammy scenario: As the climate gets warmer, microbes in peatlands produce more methane, while other microbes in peat moss become less able to consume the greenhouse gas. “We could get an explosion of methane much more than we can predict,” Kostka says.
Information about plant microbiomes is scant. Most plants whose microbiomes are being studied are crops, like corn and soybeans. “Few studies are available on plants that are environmentally important but not so economically important,” Kostka says. “A lot of our work is to build better models for how these wetlands respond to climate change.”
“Few studies are available on plants that are environmentally important but not so economically important. A lot of our work is to build better models for how these wetlands respond to climate change.”
Georgia Tech’s Glass will study the geochemical aspects of the peat moss microbiome. She will measure how fast peat moss microbes fix nitrogen and consume methane. She will also identify the trace nutrients available to peat moss in the wetland.
“Because these peatlands receive most of their nutrient input from precipitation, they contain extremely low concentrations of some bioessential trace metals,” Glass says. “We're interested in testing how trace nutrient availability impacts the growth of methane-cycling microbes exposed to warming temperatures.”
At Lawrence Livermore National Laboratory, Mayali will use NanoSims, an imaging mass spectrometer, to identify what microbes are eating the methane or fixing nitrogen. He will incubate microbe samples with substrates – methane, carbon dioxide, and nitrogen – enriched in rare isotopes such as carbon-13 instead of the normally abundant carbon-12. Analysis by NanoSims creates isotope maps that enables detailed tracing of who did what.
“Our instrument is able to not only track who is eating the methane or fixing nitrogen from the air, but more importantly, how much and where it ultimately ends up, for example into the Sphagnum plant versus being kept by the microbes,” Mayali says.
Meanwhile, at Oak Ridge National Laboratory, Weston will use genetically characterized peat moss and microbial members to construct synthetic communities to test how host moss genes influence microbiome assembly and functioning. “Peat moss microbiomes are extremely complex with thousands of members with diverse metabolic capabilities,” Weston says.
“To help determine the role of specific community member interactions,” Weston adds, “we will decompose the field system into simplified synthetic communities where community changes and nutrients can be accurately measured and subjected to precise environmental manipulations.”
“We can engineer wetlands to encourage the growth of peat moss, but that’s not our goal,” Kostka says. “Our project is fundamental science. We’re trying to figure out how the microbes help the plants grow better.”
Episode 4 of ScienceMatters' Season 1 stars Nastassia Patin. Listen to the podcase here and read the transcript here!
Massive whale sharks headline the Ocean Voyager exhibit at Georgia Aquarium. Its tiniest residents are the ones that concern Nastassia Patin. Patin is a postdoctoral researcher working in the lab of Frank Stewart. Stewart is an associate professor in the School of Biological Sciences and a member of Georgia Tech's Parker H. Petit Institute for Bioengineering and Bioscience.
Patin's research interests are microbial ecology, environmental microbiology, chemical ecology, metagenomics. Episode 4 describes her findings after studying the microbiome of the Ocean Voyage exhibit at Georgia Aquarium. What she’s learning may help keep all aquariums clear and healthy.
Take a listen at sciencematters.gatech.edu.
Enter to win a prize by answering the question for Episode 4:
What is the name of the Georgia Aquarium sea turtle mentioned in Episode 4?
Submit your entry by 11 AM on Monday, Sept. 17, at sciencematters.gatech.edu. Answer and winner will be announced shortly after the quiz closes.
Conan Zhao is the winner of ScienceMatters Episode 3 quiz.
ScienceMatters Episode 3 features M.G. Finn, chair of the School of Chemistry and Biochemistry. Finn described his efforts to create a vaccine against the dreadful parasitic disease leishmaniasis.
The quiz question was: What sugar molecule mentioned in Episode 3 is the main reason surgeons can’t transplant organs from animals into humans?
The answer is in the rest of the story, here.
Anyone lost in a desert hallucinating mirages knows that extreme dehydration discombobulates the mind. But just two hours of vigorous yard work in the summer sun without drinking fluids could be enough to blunt concentration, according to a new study.
Cognitive functions often wilt as water departs the body, researchers at the Georgia Institute of Technology reported after statistically analyzing data from multiple peer-reviewed research papers on dehydration and cognitive ability. The data pointed to functions like attention, coordination and complex problem solving suffering the most, and activities like reacting quickly when prompted not diminishing much.
“The simplest reaction time tasks were least impacted, even as dehydration got worse, but tasks that require attention were quite impacted,” said Mindy Millard-Stafford, a professor in Georgia Tech’s School of Biological Sciences.
Less fluid, more goofs
As the bodies of test subjects in various studies lost water, the majority of participants increasingly made errors during attention-related tasks that were mostly repetitive and unexciting, such as punching a button in varying patterns for quite a few minutes. There are situations in life that challenge attentiveness in a similar manner, and when it lapses, snafus can happen.
“Maintaining focus in a long meeting, driving a car, a monotonous job in a hot factory that requires you to stay alert are some of them,” said Millard-Stafford, the study’s principal investigator. “Higher-order functions like doing math or applying logic also dropped off.”
The researchers have been concerned that dehydration could raise the risk of an accident, particularly in scenarios that combine heavy sweating and dangerous machinery or military hardware.
Millard-Stafford and first author Matthew Wittbrodt, a former graduate research assistant at Georgia Tech and now a postdoctoral researcher at Emory University, published their meta-analysis of the studies on June 29 in the journal Medicine & Science in Sports & Exercise.
It can happen quickly
There’s no hard and fast rule about when exactly such lapses can pop up, but the researchers examined studies with 1 to 6 percent loss of body mass due to dehydration and found more severe impairments started at 2 percent. That level has been a significant benchmark in related studies.
“There’s already a lot of quantitative documentation that if you lose 2 percent in water it affects physical abilities like muscle endurance or sports tasks and your ability to regulate your body temperature,” said Millard-Stafford, a past president of the American College of Sports Medicine. “We wanted to see if that was similar for cognitive function.”
The researchers looked at 6,591 relevant studies for their comparison, then narrowed them down to 33 papers with scientific criteria and data comparable enough to do metadata analysis. They focused on acute dehydration, which anyone could experience during exertion, heat and/or not drinking as opposed to chronic dehydration, which can be caused by a disease or disorder.
One day to lousy
How much fluid loss adds up to 2 percent body mass loss?
“If you weigh 200 pounds and you go work out for a few of hours, you drop four pounds, and that’s 2 percent body mass,” Millard-Stafford said. And it can happen fast. “With an hour of moderately intense activity, with a temperature in the mid-80s, and moderate humidity, it’s not uncommon to lose a little over 2 pounds of water.”
“If you do 12-hour fluid restriction, nothing by mouth, for medical tests, you’ll go down about 1.5 percent,” she said. “Twenty-four hours fluid restriction takes most people about 3 percent down.”
And that begins to affect more than cognition or athletic abilities and concentration.
“If you drop 4 or 5 percent, you’re going to feel really crummy,” Millard-Stafford said. “Water is the most important nutrient.”
She warned that older people can dry out more easily because they often lose their sensation of thirst and also, their kidneys are less able to concentrate urine, which makes them retain less fluid. People with high body fat content also have lower relative water reserves than lean folks.
Don’t overdo water
Hydration is important, but so is moderation.
“You can have too much water, something called hyponatremia,” Millard-Stafford said. “Some people overly aggressively, out of a fear of dehydration, drink so much water that they dilute their blood and their brain swells.”
This leads to death in rare, extreme cases, for example, when long-distance runners constantly drink but don’t sweat much and end up massively overhydrating.
“Water needs to be enough, just right,” Millard-Stafford said.
Also, she warned that while salt avoidance may be good for sedentary people or hypertension patients, whoever sweats needs some salt as well, or they won’t retain the water they drink.
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