To better understand why some cancer patients struggle to fight off infections, Georgia Tech researchers have created tiny lab-grown models of human immune systems.

These miniature models — known as human immune organoids — mimic the real-life environment where immune cells learn to recognize and attack harmful invaders and respond to vaccines. Not only are these organoids powerful new tools for studying and observing immune function in cancer, their use is likely to accelerate vaccine development, better predict disease treatment response for patients, and even speed up clinical trials. 

“Our synthetic hydrogels create a breakthrough environment for human immune organoids, allowing us to model antibody production from scratch, more precisely, and for a longer duration,” said Ankur Singh, Carl Ring Family Professor in the George W. Woodruff School of Mechanical Engineering and professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. 

“For the first time, we can recreate and sustain complex immunological processes in a synthetic gel, using blood, and effectively track B cell responses,” he added. “This is a gamechanger for understanding and treating immune vulnerabilities in patients with lymphoma who have undergone cancer treatment — and hopefully other disorders too.”

Led by Singh, the team created lab-grown immune systems that mimic human tonsils and lymph node tissue to study immune responses more accurately. Their research findings, published in the journal Nature Materials, mark a shift toward in vitro models that more closely represent human immunology. The team also included investigators from Emory University, Children’s Hospital of Atlanta, and Vanderbilt University.

Designing a Tiny Immune System Model

The researchers were inspired to address a critical issue in biomedical science: the poor success rate of translating preclinical findings from animal models into effective clinical outcomes, especially in the context of immunity, infection, and vaccine responses. 

“While animal models are valuable for many types of research, they often fail to accurately mirror realistic human immune biology, disease mechanisms, and treatment responses,” said Monica (Zhe) Zhong, a Bioengineering Ph.D. student and the paper’s first author. “To address this, we designed a new model that faithfully replicates the unique complexity of human immune biology across molecular, cellular, tissue, and system levels.”

The team used synthetic hydrogels to recreate a microenvironment where B cells from human blood and tonsils can mature and produce antibodies. When immune cells from healthy donors or lymphoma patients are cultured in these gel-like environments, the organoids support longer cell function, allowing processes like antibody formation and adaptation to occur — similar to the human body. Utilizing the organoids for individual patients helps predict how that individual will respond to infection.

The models also enable researchers to control and test immune responses under various conditions. The team discovered that not all tissue sources are the same, and tonsil cells struggled with longevity issues. They used a specialized setup to study how healthy immune cells react to signals that help them fight infections, which failed to trigger the same response in cells from lymphoma survivors who seemingly have recovered from immunotherapy treatment.

Using organoids embedded in a novel immune organ-on-chip technology, the team observed that immune cells from lymphoma survivors treated with certain immunotherapies do not organize themselves into specific “zones,” the way they normally would in a strong immune response. This lack of organization may help explain some immune challenges cancer survivors face, as evidenced by recent clinical findings. 

A Game-Changing Technology

This research is primarily of interest to infectious disease researchers, cancer researchers, immunologists, and healthcare professionals  dedicated to improving patient outcomes. By studying these miniature immune systems, they can identify why current treatments may not be effective and explore new strategies to enhance immune defenses. 

"Lymphoma patients treated with CD20-targeted therapies often face increased susceptibility to infections that can persist years after completing therapy.Understanding these long-term impacts on antibody responses could be key to improving both safety and quality of life for lymphoma survivors,” said Dr. Jean Koff, associate professor in the department of Hematology and Oncology at Emory University’s Winship Cancer Institute and a co-author on the paper. 

“This technology provides deeper biological insights and an innovative way to monitor for recovery of immunological defects over time. It could help clinicians better identify patients who would benefit from specific interventions that reduce infection risk,” Koff added.

Another critical and promising aspect of the research is its scalability: An individual researcher can make hundreds of organoids in a single sitting. The model’s capability to target different populations — both healthy and immunosuppressed patients — vastly increases its usability for vaccine and therapeutic testing. 

According to Singh, who directs the  Center for Immunoengineering at Georgia Tech, the team is already pushing the research into new dimensions, including developing cellular therapies and an aged immune system model to address aging-related questions. 

“At the end of the day, this work most immediately affects cancer patients and survivors, who often struggle with weakened immune responses and may not respond well to standard treatments like vaccines,” Singh explained. “This breakthrough could lead to new ways of boosting immune defenses, ultimately helping vulnerable patients stay healthier and recover more fully.” 

The work was initially funded by the Wellcome Leap HOPE program. This support has led to a boost in recent funding, including a recent $7.5M grant from the National Institute of Allergy and Infectious Diseases.

Citation: Zhong, Z., Quiñones-Pérez, M., Dai, Z. et al. Human immune organoids to decode B cell response in healthy donors and patients with lymphoma. Nat. Mater. (2024).

DOI: https://doi.org/10.1038/s41563-024-02037-1

Funding: Wellcome Leap HOPE Program, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Cancer Institute, and Georgia Tech Foundation

When College of Sciences External Advisory Board Chair Heidi Schindler (ABIO 1991) was a student at Georgia Tech, she struggled to find help with career opportunities in the sciences.

“Once I decided I didn’t want to go to med school or into academia, the Career Center didn’t have answers for me,” says Schindler. “I found my own way.”

As an alumna, she appreciates the emphasis now placed on student career education and makes student engagement and mentoring a priority.

“Attending events like the Student and Alumni Leadership Dinner is important to me because I don't want students to feel unsupported — like I once felt. Alumni know people. We know the business world, and we want to help students make the connections that shape their futures.”

A Networking Extravaganza

The Student and Alumni Leadership Dinner, organized by College of Sciences Career Educator Program Manager James Stringfellow and Director of Alumni Relations Leslie Roberts, is an annual event that encourages networking and promotes student and alumni engagement.

“It is our premier event,” says Stringfellow. “This year, we were fortunate to have more than 20 alumni in attendance, willing to give their time and expertise to help students prepare for securing a career.”

Attendees included students from all six schools in the College of Sciences. First-year Matthias Keys is a biology major.

“I’m here to gain knowledge and wisdom,” says Keys. “There’s so much to learn from alumni working in the real world.”

Maddie Tibaldi is a fourth-year neuroscience major. “I’ve heard so much about the strength of Georgia Tech’s alumni network. I’m enjoying talking to alums and learning what activities I can do to enhance my professional development.”

Double Jacket Ralph Cullen (PSY 2008, M.S. Human Factors Psychology 2008) attended the Leadership Dinner for the fourth time.

“I enjoy interacting with the students,” says Cullen, a research manager for the quant team at Etsy. “Since I frequently interview job candidates, I can pass on what I look for in a resume and what impresses me in interviews.”

A Big Event with Small Groups

The event kicked off with a special 30-minute session facilitated by Dean of the College of Sciences and Betsy Middleton and John Clark Sutherland Chair Susan Lozier who discussed current and future goals for the College and answered questions from students and alumni.

"I’m inspired by the enthusiasm and energy I’ve seen tonight," says Lozier. "In the College of Sciences, we believe in learning that extends beyond the classroom, and our alumni are a vital part of that experience. Their insights can help our students bridge the gap between academic theory and professional practice."

The evening’s activities included Networking Bingo and Speed Networking. The Networking Bingo icebreaker helped alleviate students’ nervousness by providing specific questions to ask alumni. For the speed networking activity, students rotated between tables to talk with alumni about topics such as what they wished they had known in college, making good career decisions, negotiating workplace conflicts, and how to get hired in the real world.

Georgia Tech Career Center Executive Director David Gaston applauded the collective team effort it takes to launch students into professional careers.  

“From faculty and staff to alumni and industry partners, every member plays a crucial role in providing the support, guidance, and opportunities our students need to thrive in their chosen fields,” says Gaston. “ The College of Sciences Student Alumni Leadership Dinner is instrumental in bringing our partners together to allow students to meaningfully engage with professionals in careers they may want to pursue. ”

2024 Internship Company of the Year

During the festivities, Stringfellow announced the inaugural winner of the Internship Company of the Year, BrandSafway. The award honors a company that provides a high-quality learning environment for student interns.  

Lauren Hester, who graduated this past August with a psychology degree, interned with BrandSafway as a Workday case management intern and nominated them for the award.

“It was my first corporate experience and BrandSafway was such a welcoming environment,” says Hester. “There were no dumb questions. I was able to be a sponge and learn so much about how business works. Thank you to BrandSafway for opening that door so I could learn and grow, not just as a scientist, but as someone who is now business savvy.”

BrandSafway President and CEO Karl Fessenden accepted the award.

“We are based in Atlanta and appreciate the benefit of having a world-renowned Institute just 20 minutes from our doors,” says Fessenden. “What we value most about our internship program is that it brings in students who are not only technically skilled but also bring fresh perspectives and innovative ideas to our organization. We are a better company because of our internship program.”

When presenting the award, Hester related that she heard about the internship at a networking event hosted by the College of Sciences and the Career Center:

"Networking really does pay off!”

A wellness course at Georgia Tech was redesigned for the fall to help first-year students better navigate the challenges of college life. The course, APPH 1040: Scientific Foundations of Health, expands the Institute’s First-Year Wellness Experience (FYWE), which promotes student wellness across multiple areas.

“This course bridges the academic and well-being experiences of the student,” says Christie Stewart, co-director of the wellness course and senior academic professional in the School of Biological Sciences. “We designed it to help students develop habits that support their overall success, both in and out of the classroom.”  

Teaching Wellness from Day One 

APPH 1040 gives students practical strategies they can apply immediately. The course now covers topics like sleep improvement, stress management, resilience, and social wellness to help students better adapt to college life. 

Becky James, one of the course instructors, encourages students to take a holistic approach. “Students are empowered to take a whole-person perspective and explore how wellness dimensions relate, overlap, and play a role in their well-being,” says James.  

First-year mechanical engineering student Gargi Telang says the course is reshaping her perspective. “Each lecture focuses on a different aspect of wellness,” she says. “My professor doesn’t just tell us what to do — she explains why. This approach has completely transformed my mindset. I wish I could take this course every semester at Tech. You show up, you reap the benefits.”   

Fostering Community and Belonging

In addition to individual wellness, the course emphasizes building social connections. “Social wellness is about creating a community. It’s important that students connect to their classmates and find a sense of belonging,” says Stewart. “With a focus on mental health both campus-wide and nationwide, we needed to take a closer look at our culture of wellness and how we can build that on campus.”  

First-year computer science student Ella Foster says the focus on collaboration and self-discovery is one of the course’s strengths. “I love how we are working together to establish roles for our research projects based on our CliftonStrengths Assessments — a tool that helps people identify their natural talents.” 

Strengthening an Established Program

Faculty redesigned the curriculum of the existing APPH 1040 course to better align with FYWE and the eight key dimensions of well-being (financial, spiritual, environmental, intellectual, emotional, social, physical, and occupational well-being). Supported by partnerships with Housing and Residence Life, the Center for Mental Health Care and Resources, and the Wellness Empowerment Center, the FYWE provides a range of services designed to promote student well-being, including peer support networks and designated residence halls.  

“Many first-year students face stress related to academic rigor, making it essential to introduce them to wellness strategies early in their college careers,” says Stewart.  

This year, the new APPH 1040 piloted two cohorts of 48 students each — one on the east and west side of campus. Feedback through student surveys will help improve future courses.  

“The first year is an integral part of a student’s foundation for success,” says School of Biological Sciences Lecturer Sasha McBurse. “By the completion of this course, students will have strategies to overcome adversity and a game plan for improving their wellness for life.”  

First-year computer science student Ayden Beard says this semester was the perfect time for him to take the course. “It’s given me so many tips on ways to develop healthy habits, manage stress, and maintain a happy, healthy life.”  

The course will be offered again in the spring. 

You can find more information on Georgia Tech’s wellness programs and events here and the School of Biological Sciences’ wellness courses here.   

 From sending cancer into remission to alleviating Covid-19 symptoms, immunotherapy can provide revolutionary disease treatments. Immunotherapies use antibodies — proteins that bind to cell markers called antigens — to target and eliminate the antigen. But despite how effective immunotherapy can be, it isn’t widely used because finding the right antibodies to develop treatments is challenging, time-consuming work.

Georgia Tech researchers are making this process a little easier, though. Their new tool, AF2Complex, used deep learning to predict which antibodies could bind to Covid-19’s infamous spike protein. The researchers created input data for the deep-learning model using sequences of known antigen binders. This method correctly predicted 90% of the best antibodies in one test with 1,000 antibodies and was recently published in Proceedings of the National Academy of Sciences. Treating Covid-19 is just the start of its potential. 

“AF2Complex improves therapeutic development,” said Mu Gao, a senior research scientist in the School of Biological Sciences (SBS). “If you have a high-quality model, then you can tinker with the protein sequence and optimize the antibody, making it more suitable for drug development.”

Developing the Deep-Learning Model

The researchers weren’t the first to use deep learning to predict protein structures, but they did considerably expand the model’s capabilities. In 2020, the Nobel Prize-winning DeepMind AlphaFold, an Alphabet project, made breakthroughs using deep learning to predict the protein structures of single proteins. Georgia Tech researchers pushed the model to predict the structures of protein complexes. In 2021, they created the first version of AF2Complex, which could predict interactions between multiple, complex proteins like E. coli. Applying it to human proteins was the next step — but much harder.

“Normally, when you predict protein-protein interactions, the surface area of the protein is quite large, so you could afford to make a few mistakes with an imperfect model,” said Jeffrey Skolnick, a Regents’ Professor and the Mary and Maisie Gibson Chair in SBS and a Georgia Research Alliance Eminent Scholar.  “But an antibody-protein interaction occupies a much smaller interfacial area. Imagine going from hitting a big target anywhere to hitting the bullseye.”

Determining how to predict the antibody-antigen interactions was the biggest challenge. The researchers focused on the Covid-19 virus because it had many complex antigen-binding sequences and epitopes, the specific molecule region that interacts with B- and T-cells to trigger an immune response. Covid-19 also was a widely available dataset, unlike many immunotherapies to which only pharmaceutical companies have access. The Covid-19 database, in effect, offered a rich training environment for the AF2 algorithm. 

Skolnick and Gao used Covid-19 sequences from known antibodies to identify evolutionary relationships and patterns, improving the accuracy of predictions. From there, they applied the AF2 deep-learning model, already trained on a vast amount of protein structure data. The model used sequences to predict how proteins fold and interact, developing a 3D structure of protein complexes. Plus, it could produce 3D structures for more than just one dominant epitope.

The predictions were validated against experimental data, refining the model. With these predicted structures, researchers can do everything from better understanding biological processes to developing new drugs.

Treating the Virus of the Future

The researchers believe deep-learning technologies could revolutionize how we treat future diseases. With infinite resources and time, researchers could manually try every antibody-antigen combination, but no scientist has that. AF2Complex can narrow the focus and get to the treatment sooner. 

“Imagine the virus from hell arises. You could design a series of antibodies using this algorithm, so it cuts down the time for vaccine development,” Skolnick said. “There are no substitutes for a real experiment, but AF2Complex can prioritize which experiments you should do, so you have more shots at the goal.”

The researchers are already collaborating with Emory University to conduct experiments that validate AF2Complex’s findings. They also are pursuing a path to commercialize the model. When the next pandemic starts, we will be better prepared.

The  National Institutes of Health provided, and the Department of Energy and National Science Foundation supported, the main computing resources.