For the second consecutive year, a Georgia Tech student and their advisor have been awarded a Howard Hughes Medical Institute (HHMI) Gilliam Fellowship for Advanced Study. Autumn Peterson, a Ph.D. student in biology, will receive $53,000 per year for up to three years for dissertation research. Peterson’s advisor, William Ratcliff, will participate in activities that address challenges to diversity and inclusion at the graduate level.

“Receiving the HHMI Gilliam award will allow me to conduct innovative research while building leadership and mentorship skills–all attributes that are necessary to become a better scientist,” said Peterson. “Ultimately, this will help me prepare for a career in academia as a professor.”  

HHMI awards student-advisor pairs based on the student’s potential for scientific leadership and the advisor’s commitment to a culture of inclusion in academia.  

“Through my academic journey at Virginia Tech, University of Kansas, and Georgia Tech, I have had wonderful mentors and colleagues, but I have had few Black faculty role models,” said Peterson. “It wasn’t until I worked with Brian Atkinson, an African American professor at the University of Kansas, that I even considered becoming a professor. That research experience put me on a path that led directly to Tech and underscored my commitment to outreach broadening participation in science. I am looking forward to being a part of the HHMI community and fostering leadership and mentorship skills that will help me succeed in my career in academia so I can be a role model for future generations of students.”  

The program awards grants to dissertation advisors and encourages the grantee institution and the advisor to facilitate institutional changes to create environments that advance diversity and inclusion.  

“As an advisor, I’m delighted to see Autumn’s work and leadership recognized this way,” said Ratcliff, an associate professor in the School of Biological Sciences and co-director of the Interdisciplinary Ph.D. in Quantitative Biosciences at Georgia Tech. “This fellowship is also a huge opportunity for us to do cool science, become better scientists and mentors, and work to improve diversity and inclusion at Georgia Tech. I cannot wait to get to know the broader community of Gilliam Fellows and mentors.”  

As part of the Gilliam Award, the advisor will also complete a year-long culturally responsive mentorship skills development course.  

“This fellowship provides key resources and professional opportunities that I think can make me a better advisor and can support our work on behalf of trainees from underrepresented groups at Georgia Tech more broadly,” said Ratcliff.  

Fellows are required to participate in the Gilliam Annual Meeting, Gilliam Leadership Training course, and one HHMI Science Meeting per year in the second and third years of the fellowship award where there will be Gilliam-specific discussion sessions.  

Learn more about the HHMI Gilliam Fellows program here. 

With the sequencing of the human genome, scientists say personalized medicine is a more realistic goal. A future of customized medications, better understanding about disease factors and individualized risks, and a deeper knowledge of how cell mutations result in diseases like cancer could help pave the way for healthier populations around the globe.

But to realize this future, scientists need to build better risk assessments containing as much genetic information as possible regarding human populations — without compromising security and privacy, and without marginalizing or overrepresenting any groups. To date, existing datasets of this type of information have largely focused on individuals of European ancestry — which has meant that most people in the world have either been critically underrepresented, or at times not represented at all, among these important genomic studies and resources. 

Many groups are working together to improve those datasets, including School of Biological Sciences Patton Professor Greg Gibson, who recently teamed up with Emory University School of Medicine’s Subra Kugathasan, M.D. and other colleagues to publish a new study based on what Gibson shares as the largest whole genome-sequencing study of inflammatory bowel disease for African-Americans to date. 

“Whole-Genome Sequencing of African-Americans Implicates Differential Genetic Architecture in Inflammatory Bowel Disease,” published February 17 in the American Journal for Human Genetics, researches inflammatory bowel disease (IBD) and Crohn’s disease in more than 3,000 Americans of African descent. IBD patients made up 1,774 members of the group, while the control group numbered 1,644 individuals without IBD. 

“The huge concern in the field is that all minorities are dramatically underrepresented” in genetic studies, Gibson notes, underscoring the need for more diverse studies and highlighting his interest in pursuing the current study. “It’s comprehensive, it’s incredibly powerful and it way overperforms what came before, in terms of magnitude of accomplishment. We started three years ago, which I think is pretty amazing. There are still not many studies out there as large in terms of true genomic sequencing of population.”

The group’s work hopes to build a better understanding of potential population divergence and genetic risk of specific complex diseases like IBD — as well as identify any possible corresponding evolution of susceptibility and origins of health disparities.

To achieve this, the research group set out to further resolve the genetic architecture of inflammatory bowel disease — and also to better define the differential genetic structure of the disease across divergent ancestries. The team notes that their resulting analyses “include many alleles that were not previously examined, in a population that remains very significantly understudied.”

So, what exactly is an allele?

A brief tutorial on alleles and genomics

Alleles are alternative forms of a gene, and they’re born from mutations. “Every person’s genome has about a million out of a billion pairs that are different,” Gibson explains. These are polymorphisms, or alleles, which are “the flavor of a gene.” When a new mutation happens, its frequency is extremely rare, but some mutations do become more common over time, and contribute ever so subtly to disease.

Most of these alleles are shared by European and African-Americans, but small differences in frequency and effect can add up — especially over several thousand of them — to real differences in risk of disease progression.

Gibson also highlights the importance of understanding and taking into account the many environmental factors that can be related to IBD and Crohn’s, such as stress, diet, access to quality nutrition, access to healthcare and preventative medicine, and even differences in socioeconomic status and opportunities that also tally up to significant health and risk disparities across divergent populations.   

More diverse genomics assessments coming soon?

Gibson and Kugathasan’s research was a collaborative study involving self-identified African-American subjects recruited from five primary sites across the country: Emory University (recruited as part of the Emory African-American Inflammatory Bowel Disease Consortium), Johns Hopkins/Rutgers (recruited as part of the Multicenter African-American Inflammatory Bowel Disease Study), Cedars Sinai Medical Center, Mount Sinai Medical Center, and Washington University (recruited as part of the Centers for Common Disease Genomics network). 

The study was approved by the institutional review boards at each of the participating sites and informed consent was obtained from all the participants. To protect privacy, de-identified datasets including genetic data were housed at Emory University with the approval of the local ethical board.

All DNA samples investigated in the study (a total of 3,610 before quality control) were processed and sequenced at the Broad Institute of Harvard and the Massachusetts Institute of Technology following the same protocol.

More of this needs to happen, Gibson notes, so that the real work on narrowing the gaps and differences in healthcare among a diverse spectrum of populations can begin. He adds that the African genetic structure requires complete gene sequencing for all sorts of technical reasons, making it harder than more studies of Europeans — as well as essential and well worth the effort. 

“If you try to predict the onset of disease and you don’t account for ancestry differences, your assessments are just way off. In any sort of medicine, you want to be as accurate as you can. That’s why it’s so critical to include diversity in genetic studies as we progress to equitable access of all health care in all populations.”

Gibson says his next research study will deal with how genetics interacts with the other factors involved in health in underrepresented communities, such as nutrition and the impact of so-called “food deserts,” environmental issues, access to important health care, and other socio-economic indicators. 

“It’s probably the most important paper I’ll ever work on,” he says. 

The recently announced College of Sciences Strategic Plan: 2021-2030 has three ambitious goals at its foundation, each of which are focused on striving for excellence — in the workplace, in training and education, and in research. A trio of themes connect across the plan’s goals to guide this work and strategy: catalyze discovery and solutions, amplify the College’s impact, and build communities of excellence. Explicit in the strategic plan are expectations and goals to enhance inclusivity, equity, and diversity, especially of underrepresented groups in the College.

In January of this year, the College released a call for proposal submissions that reflect these themes and accomplish these goals. At that time, all students, staff, and faculty in the College’s community were encouraged to work in collaborative and interdisciplinary teams to submit proposals for projects.

Collective funding to achieve the proposals is provided through a generous $300,000 investment by the Betsy Middleton and John Clark Sutherland Dean's Chair. “I can think of no better use of the Sutherland Chair funds than to invest in ideas from our community. I expect this investment to pay dividends in the years ahead,” notes Susan Lozier, College of Sciences Dean and Betsy Middleton and John Clark Sutherland Chair.

“We were gratified to receive a large number of proposals from across the College of Sciences community, including proposals led by students, staff, and faculty,” says Julia Kubanek, Associate Dean for Research in the College of Sciences, and a professor in the School of Biological Sciences and the School of Chemistry and Biochemistry. “Each of the strategic plan goals are represented among the proposals we received. All proposals were group efforts, and many represented interests from members of different academic programs and schools within our college. Among the proposals received, members of all six of our schools participated.”

“These projects and programs will lay the groundwork for meeting the goals of our strategic plan,” Kubanek adds. The dozen new projects include team-building efforts for collaborative research, staff professional development, recruitment of underrepresented minorities into academic programs and postdoctoral training, and several other initiatives:

Astrobiology Program
PI (Principal Investigator): Jennifer Glass, associate professor in the School of Earth and Atmospheric Sciences
Research (Astrobiology); Communities of Excellence

Center for Microbial Dynamics & Infection Postdoctoral Recruitment Program
Co-PIs: Sam Brown, professor in the School of Biological Sciences and Marvin Whiteley, professor in the School of Biological Sciences, Georgia Tech Bennie H. and Nelson D. Abell Chair in Molecular and Cellular Biology, Georgia Research Alliance Eminent Scholar, and Co-Director, Emory-Children’s CF Center (CF@LANTA)
Research (Microbial Dynamics and Infections); Communities of Excellence; Diversity/Inclusion (Historically Underrepresented Groups)

Deliberate Innovation in Undergraduate Biology
PI: Chrissy Spencer, senior academic professional in the School of Biological Sciences
Education/Training; Amplify Impact

Empowering Strengths-Based College of Sciences Team Members
PI: Christie Stewart, academic professional in the School of Biological Sciences
Communities of Excellence

ENTANGLED (Graduate Students in Quantum Sciences)
PI: Martin Mourigal, associate professor in the School of Physics
Research (Quantum systems); Education/Training; Communities of Excellence

Georgia Tech Summer Research Academy (SRA)
PI: Shania Khatri, undergraduate research assistant and Stamps President's Scholar in the School of Biological Sciences
Education/Training; Undergraduate Recruitment; Communities of Excellence; Diversity/Inclusion

Initiative for Living Dynamic Systems
Co-PIs: Simon Sponberg, Dunn Family Associate Professor of Physics and Biological Sciences and Daniel Goldman, Dunn Family Professor of Physics
Research (Physics of Movement); Growing Faculty Leadership; Communities of Excellence

Strategic Development at the Interface of Human and Environmental Health
Co-PIs: Joshua Weitz, Patton Distinguished Professor in the School of Biological Sciences and co-director of the Interdisciplinary Ph.D. in Quantitative Biosciences and Greg Gibson, Patton Distinguished Professor in the School of Biological Sciences, Director of the Center for Integrative Genomics, and Genome Analysis core of the Petit Institute for Bioengineering and Bioscience
Research; Growing Faculty Leadership; Communities of Excellence

Nucleating Artificial Intelligence and Machine Learning Collaborations in the College of Sciences
PI: Roman Grigoriev, professor in the School of Physics
Research (Data Science); Growing Faculty Leadership; Communities of Excellence

Project Potty Parity
PI: Mike Schatz, interim chair and professor in the School of Physics
Communities of Excellence; Diversity/Inclusion

Staff Advisory Council Strategic Plan Proposal
PI: Kathy Sims, development assistant in the College of Sciences, chair of the College of Sciences Staff Advisory Council, and member of the College of Sciences Task Force for Racial Equity
Communities of Excellence

Urban Heat Islands
PI: Kim Cobb, Georgia Power Chair, ADVANCE Professor, and Director of the Global Change Program at Georgia Tech
Research (Climate science); Education/training; Communities of Excellence; Diversity/Inclusion

Learn more about the College of Sciences Strategic Plan: 2021-2030 and coordinating Implementation Guide.

It may not be a process that most people are familiar with, but DNA methylation is very important to brain evolution. It’s viewed as a critical regulatory mechanism implicated in cognitive development, learning, memory, and disease. That regulation includes gene expression, which happens when DNA instructions are converted into a functional product, namely messenger RNA molecules, which provide templates for proteins.

A School of Biological Sciences professor who specializes in molecular and genomic evolution has uncovered some new information about how DNA methylation evolved in the human brain — and how that compares to brains of some of our primate relatives. She and a global team of researchers have published their findings, “Evolution of DNA methylation in the human brain” in Nature Communications. 

“The large and complex brain is a distinguishing trait of the human lineage,” explains Soojin Yi, who directs the Yi Lab of Comparative Genomics and Epigenomics at Georgia Tech. “Scientists have been very interested in finding genetic and gene expression changes that are associated with the evolution of human brains.”

DNA methylation is a biological process by which methyl groups — organic compounds made up of three hydrogen atoms and a carbon atom — are added to DNA, which in turn sets off molecular processes to help regulate gene expression and other genetic factors that are necessary in healthy brains and nervous systems. When something goes wrong with DNA methylation, it can lead to certain diseases, including cancer and neuropsychiatric conditions such as schizophrenia.

“To understand the contribution of DNA methylation to human brain-specific gene regulation and disease susceptibility, it is necessary to extend our knowledge of evolutionary changes in DNA methylation during human brain evolution,” Yi says. 

Science has long known about the DNA methylation connection to certain conditions, but the evolutionary aspect has so far been largely unexplored. “Previous studies used bulk tissues, while DNA methylation is known to vary substantially between cell types,” Yi shares, so her team, including the paper’s co-corresponding author Genevieve Konopka’s lab at UT Southwestern Medical Center, focused on the search for cell-type-specific epigenetic (gene-activity-changing) marks, including DNA methylation and histone (basic protein) modifications. Those are implicated in cell-type-specific gene expression and disease susceptibility in humans. 

“Data from bulk tissues can be biased toward specific cell types and consequently, underpowered to detect cell-type-specific evolutionary changes,” Yi explains. “Therefore, to fully understand the role of DNA methylation in human brain evolution, it is necessary to study cell-type-specific changes of DNA methylation.”

Yi and her team found suitable samples for chimpanzees and macaques in the specimen archives of the Yerkes National Primate Research Center at Emory University. “We also separated neurons and oligodendrocytes (which forms the protective sheaths for neural transmission) from bulk brain samples, so that we can study cell-type specific patterns of DNA methylation,” Yi says.

“We found that the human brains are particularly heavily methylated compared to chimpanzee and rhesus macaque brains — both in neurons and oligodendrocytes.” 

Yi and her team found that some positions that have unique patterns of DNA methylation in human brains were previously implicated in neuropsychiatric diseases including schizophrenia.

“Our work extends the knowledge of the unique roles of . . . methylation in human brain evolution, and offers a new framework for investigating the role of the epigenome evolution in connecting the genome to brain development, function, and diseases.” 

Yi’s research team included colleagues from the Yerkes National Primate Research Center, and the Department of Pathology, at Emory University; the Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Spain; The Department of Neuroscience at UT Southwestern Medical Center;  the Center for Medical Research and Education, Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Japan; the Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Metropolitan Institute of Medical Science, Japan; and the College of Nursing, The Research Institute of Nursing Science, Seoul National University, South Korea.

For human samples, UT Southwestern Medical Center Institutional Review Board (IRB) has determined that as this research was conducted using post-mortem specimens, the project does not meet the definition of human subjects research and does not require IRB approval and oversight. Non-human primate samples were obtained from archival, post-mortem brain tissue opportunistically collected from subjects that died from natural causes, and following procedures approved by the Emory Institutional Animal Care and Use Committee and in accordance with federal and institutional guidelines for the humane care and use of experimental animals. No living great apes were used in this study. 

Getting an itch is one thing. Everybody has to scratch every now and then, and some of us have to watch out for dry skin during the winter, or allergic reactions to ingredients in certain makeup or lotions. Yet for most of us, those discomforts involve itches on parts of our skin that have hair, not on what is called ‘glabrous’ skin: the smoother, tougher skin that’s found on the palms of your hands and the soles of your feet.

And those glabrous skin conditions often cause chronic itching and pain. In the U.S., there are an estimated 200,000 cases of dyshidrosis, a skin condition causing itchy blisters to develop only on the palm and soles, each year. Another chronic skin condition, palmoplantar pustulosis (a type of psoriasis which causes inflamed, scaly skin and intense itch on the palms and soles) affects an estimated 330,0000 to 1,650,000 people in the U.S. each year.

“Those patients with chronic itch suffer a lot. They don’t have a significant treatment, and it affects their lives,” says Liang Han, an assistant professor in the School of Biological Sciences who also researches in the Parker H. Petit Institute for Bioengineering and Bioscience. Now, new research from Han and students in her Han Lab at Georgia Tech may offer a balm of hope for these patients. 

"MrgprC11⁺ sensory neurons mediate glabrous skin itch,” published in the science journal PNAS (Proceedings of the National Academy of Sciences of the United States of America), is co-authored by Han alongside current and former graduate students Haley R. Steele (first author), Yanyan Xing, Yuyan Zhu, Henry B. Hilley, Katy Lawson, Yeseul Nho, and Taylor Niehoff.

Han and her students uncovered new information about which sensory neurons are responsible for glabrous skin itch. “We here present evidence demonstrating that distinct neuronal populations are responsible for mediating hairy and glabrous skin itch,” the authors write. “This study advanced our understanding of itch and will have significant impact on the clinical treatment of itch.”

Steele adds more: “Our research is showing, for the first time, the actual neurons that send itch are different populations. Neurons that are in hairy skin that do not sense itch in glabrous skins are one population, and another senses itch in glabrous skins.”

Of transgenic mice and sensory neurons

Steele, a current graduate student in the School of Biological Sciences who dual-majored in Biology and Literature, Media, Communications, is in her fifth year at Georgia Tech. In the new study, she highlights another reason why glabrous skin itches are significant sources of pain for patients. “That’s actually one of the most debilitating places (to get an itch),” Steels says. “If your hands are itchy, it’s hard to grasp things, and if it’s your feet, it can be hard to walk. If there’s an itch on your arm, you can still type. You’ll be distracted, but you’ll be okay. But if it’s your hands and feet, it’s harder to do everyday things.”

Why has an explanation so far eluded science? “I think one reason is because most of the people in the field kind of assumed it was the same mechanism that’s controlling the sensation. It’s technically challenging. It’s more difficult than working on hairy skin,” Han says.

She and her team got around the technical challenge by relying on a new investigative procedure, or assay, that Steele had been working on to judge behavior in research mice. The previous method would have involved injecting itch-causing chemicals into mice skin, but the majority of a mouse’s skin is covered with hair. The team had to focus on the smooth glabrous skin on tiny mice hands and feet. 

Using transgenic (genetically modified) mice also helped track down the proper sensory neurons responsible for glabrous skin itches. “What we can do is specifically activate a particular set of neurons that causes itch, and we saw that biting behavior again modeled,” referring to how mice usually deal with itchy skin.

A particular set of mice in the study was given a chemical to specifically kill an entire line of neurons. “We can see what would happen if they didn’t have those neurons we’re targeting,” Steele adds. 

Han, Steele and their team focused on three previously known pruriceptive (related to itch sensation) neurons in glabrous skin.

The result, as highlighted in the research study: “Our results show that MrgprA3⁺ and MrgprD⁺ neurons, although key mediators for hairy skin itch, do not play important roles in glabrous skin itch, demonstrating a mechanistic difference in itch sensation between hairy and glabrous skin. We found that MrgprC11⁺ neurons are the major mediators for glabrous skin itch. Activation of MrgprC11⁺ neurons induced glabrous skin itch, while ablation (removal) of MrgprC11⁺ neurons reduced both acute and chronic glabrous skin itch.”

Applications could involve figuring out a way for patients to turn off those itch-inducing neurons. “Blocking the neuron is one approach, but that’s down the road. That is something that we always hope,” Han says. “It is very reasonable to propose — to find a way to block those neurons in human skin.”

The researcher team thanks the animal care and welfare team at Georgia Institute of Technology for their care and services. This work was supported by grants from the U.S. National Institutes of Health (NS087088 and HL141269), and the Pfizer Aspire Dermatology Award to Liang Han.