The UAB Department of Microbiology is a hub of groundbreaking research, tackling some of the most pressing challenges in the field. In the first part of this series, we explored how the department established itself as a leading force in microbiology, with pioneering contributions to combat the HIV/AIDS epidemic of the 1980s.

Part two highlighted their remarkable advancements in scientific research and public health from the late 1990s to the present day. Now, in this final part, we examine how these discoveries are shaping the future of the department and the broader field of microbiology.

From investigating high-risk microbes like tuberculosis and pneumonia to using advanced cryo-electron microscopy to visualize disease-causing proteins, the department continues to lead the way in scientific discovery.

“Microbiology addresses some of the most significant challenges impacting human health, including antimicrobial resistance, emerging infectious diseases, environmental microbial threats, foodborne illnesses, and microbial biotechnology and biosecurity,” explained J. Victor Garcia-Martinez, Ph.D., professor and chair in the UAB Department of Microbiology. “Our department is tasked with preparing the next generation of individuals capable of taking on these threats. Sometimes, we don’t realize that they are present in our own backyard, like the recent discovery of the Camp Hill virus near Auburn [Alabama]. This new virus is related to the Hendra and Nipah viruses. The Hendra and Nipah viruses are known to cause severe respiratory illness and encephalitis in humans, with mortality rates of 40 percent to 70 percent.”

Allan Zajac, Ph.D., professor; Jessica Scoffield, Ph.D., associate professor; Gurkan Mollaoglu, Ph.D., assistant professor; and Garcia-Martinez, offer invaluable insights into the department's ongoing innovations and the future of microbiology research.

Cutting-edge research and advanced technology

Having evolved from its founding with just three faculty members in 1945, the department, now boasting more than 30 faculty, is an active research hub with a wide range of advanced research projects underway.

“We are a large, dynamic department with groundbreaking research taking place in numerous areas,” Zajac said. “We are developing new techniques to model viral diseases and improve organ transplant success—and that’s just the start.”

Expanding on this progress, the department is leveraging innovative technologies to tackle some of the most pressing challenges in microbiology and infectious diseases.

"Scientists in our department are incorporating advanced technologies such as single-particle cryo-electron microscopy, nuclear magnetic resonance, single-cell RNA sequencing, spatial proteomics, and 3D mass spectrometry imaging to determine how viral and bacterial pathogens initiate and persist during infection," Scoffield explained. "These technologies will play a crucial role in developing new therapeutics to inhibit the ability of microbes to cause disease."

Furthermore, the department continues to stand as a leader in microbiology research and innovation, according to Mollaoglu.

“Our focus on unraveling fundamental virological processes—such as viral genome replication, virus-host interactions, and immune responses during infections—drives groundbreaking advancements,” he said. “These insights are instrumental in developing antiviral drugs, enhancing vaccine candidates, and creating innovative viral vectors for gene therapy and drug delivery.”

Microbial pathogenesis

The department's ongoing work in understanding the mechanisms by which bacteria and other microbes cause disease is a cornerstone of microbial pathogenesis.

“These discoveries are paving the way for improved diagnostic tools and more effective treatments for infectious diseases,” Mollaoglu said. “Several faculty members are particularly focused on exploring the structural foundations of molecules critical to viral and bacterial pathogenesis, providing valuable insights to inform the design of targeted antimicrobial drugs.”

Mollaoglu emphasized the department's focus on understanding how the host immune system responds to pathogens.

“This includes examining the activation and regulation of T and B cells, the innate immune system, and mucosal immunity,” he explained. “While these efforts reinforce our core focus on viruses and bacteria, they also extend our research scope to other significant areas, such as inflammatory and autoimmune diseases, as well as cancer.”

Through these multifaceted endeavors, the department continues to drive innovation and impact in microbiology, shaping the future of biomedical research.

Cryo-electron microscopy

Cryo-electron microscopy (cryo-EM) is a groundbreaking technique revolutionizing molecular research.

“Cryo-EM allows us to visualize these molecules at near-atomic resolution in their native, frozen-hydrated state,” Mollaoglu said. “Researchers in our department are using this powerful approach to decode the structures of viral and bacterial molecules, paving the way for innovative drug discoveries and therapeutic breakthroughs.”

This cutting-edge technology unlocks new possibilities in advancing medical research. 

Humanized mouse models

The department utilizes humanized mouse models—mice engineered with a human immune system derived from donor cells—to investigate viral and bacterial infections, organ transplantation, and cancer. “These state-of-the-art models address fundamental immunological questions and promote collaborations across various research areas within the department,” Mollaoglu explained.

These models provide UAB researchers with a controlled environment to study human immune responses, driving advancements for developing more effective treatments and therapies.

Single-cell transcriptomics

Building on the latest advancements in single-cell sequencing, several research groups are utilizing single-cell transcriptomics to investigate the molecular behavior of individual immune cells.

“This method enables us to uncover cellular heterogeneity, shedding light on the intricate mechanisms of immune cell development, differentiation, and activation,” Mollaoglu said. “These studies provide a detailed, molecular-level insight into the immune system's complexity.”

These breakthroughs establish a foundation for developing new strategies to diagnose, treat, and prevent immune-related diseases.

Spatial biology

The department is leading the way in adopting spatial biology, an innovative approach that combines proteomic and transcriptomic analyses to examine tissues at single-cell resolution within their native microenvironment.

“Spatial biology provides unique insights into healthy and diseased states,” Mollaoglu stated. “By combining this with CRISPR technology, our team investigates how cancer genes influence the immune microenvironment, aiming to develop novel immunotherapies that could change the landscape of cancer treatment.”

This breakthrough opens the door for future clinical trials combining two FDA-approved drugs: Dupixent (an IL-4 receptor blocker) and Keytruda or Opdivo (PD-1 inhibitors). Mollaoglu and colleagues utilized cutting-edge spatial biology techniques to investigate how heterogeneous tumors create immune niches that promote clonal tumor evolution and resistance to immunotherapy. Their pioneering research uncovered that targeting IL-4 signaling can sensitize ovarian cancer cells to immune checkpoint blockade.

This progressive approach advances the understanding of cancer and offers exciting possibilities for next-generation therapies.

Recent research discoveries

New BKPyV replication model

Sunnie Thompson, Ph.D., an associate professor in the UAB Department of Microbiology, recently published a discovery that may improve kidney transplantation. She employed a “single-cell virology” technique to explore how BK polyomavirus produces more viruses.

While this infection may be unfamiliar, nearly all adults carry the virus—typically harmless—until a kidney transplant is needed. After transplantation, the virus can reactivate, leading to significant organ rejection. Thompson’s study has made groundbreaking strides in understanding the early stages of viral replication during reactivation, which has the potential to help develop new strategies to improve kidney transplant success rates.

Enhancing vaccine strategies with single-cell sequencing

Frances Lund, Ph.D., professor in the UAB Department of Microbiology, and her team employed single-cell sequencing to analyze memory B-cell subpopulations specific to seasonal influenza vaccines. Their research identified FcRL5+T-bet+ memory B cells as crucial predictors of long-lived antibody responses to flu vaccination, providing valuable insights for improving vaccine strategies.

Uncovering microbiota's role in infectious diseases

Angela Wahl, Ph.D., associate professor in the UAB Department of Microbiology, and Garcia-Martinez, created an innovative germ-free humanized mouse model to study the role of microbiota in human infectious diseases. Their research revealed that host microbiota enhances Epstein-Barr Virus (EBV) infection and tumorigenesis and increases mucosal HIV infection. These findings offer critical insights into the interplay between microbiota and infectious disease pathology.

Enhancing CD8 T-cell responses in chronic infections

Zajac and collaborators demonstrated that the ability of CD8 T cells to produce IL-2 during the effector phase is essential for their survival, memory formation, and resistance to exhaustion. IL-2-producing CD8 T cells attenuate IL-2-dependent STAT5 signaling, which limits terminal differentiation and enhances protective capabilities. These findings offer new insights into strategies for boosting CD8 T-cell responses in chronic viral infections.

Postdoctoral fellows drive research goals

As a research-intensive university, UAB and the Department of Microbiology are deeply committed to training the next generation of scientists. Postdoctoral fellows play a pivotal role in developing innovative technologies, generating creative research ideas, and driving forward key research initiatives.

“While the department is a community of learners, our postdoctoral fellows and students are the lifeblood of our research efforts,” Zajac said. “They work relentlessly every day to discover cures and develop new ways to prevent health threats. The constant excitement they bring and the success of watching their careers flourish—both at UAB and beyond—is a source of immense pride for all of us.”

Scoffield echoed the department’s support for its trainees.

“The department has established several mechanisms to ensure that our postdoctoral fellows are well-supported and exposed to professional development tools that will help them achieve their long-term career goals,” Scoffield said. “We are always excited to recruit motivated, hard-working, and energetic postdoctoral fellows.”

Mollaoglu added that postdoctoral fellows in the department have gone on to fill significant roles in the field.

“After completing their training, our postdoctoral alumni lead research groups in academia and industry, pushing the boundaries of science and proudly representing our department and UAB nationally and internationally,” he said. “Our leadership and faculty are deeply committed to their success, offering personalized mentoring, cutting-edge research infrastructure, targeted grant opportunities, and soft-skills training programs to prepare them for the next stages of their careers.”

The department’s unwavering investment in postdoctoral fellow training is advancing research and helping to shape the next generation of scientific leaders.

The future of microbiology research

The future of microbiology research at UAB is promising and crucial as the field continues evolving in response to emerging challenges. With a growing demand for basic and applied research, the department is strategically positioned to address critical issues like the persistent threat of new pathogens and the increasing resistance of existing human pathogens to antibiotics.

In particular, such groundbreaking work exemplifies the department’s commitment to understanding and mitigating current threats and paving the way for the future of microbiological innovation. For example, Wahl and Garcia-Martinez, along with their collaborators, identified EIDD-2801, an oral antiviral, as a potent inhibitor of SARS-CoV-2, the virus responsible for COVID-19. This discovery has the potential to redefine how antiviral therapies are developed and deployed in the fight against emerging infectious diseases.

Furthermore, microbiology research not only addresses public health issues but also drives the development of transformative technologies. For instance, Michael Niederweis, Ph.D., university professor, and his team developed a groundbreaking nanopore DNA sequencing platform based on the MspA protein from Mycobacterium smegmatis, one of the most efficient nanopores for DNA sequencing. This innovation has the potential to revolutionize the field of genomic research and transform how DNA sequencing is approached in the future.

Additionally, the study of the microbiome offers another dynamic avenue of research by exploring how the microbes in and on the human body affect health. For example, Troy Randall, Ph.D., professor, Michael Gray, Ph.D., associate professor, and Elliot Lefkowitz, Ph.D., professor, discovered that gut microbiota regulates amino acid levels, altering immune cell behavior in adipose tissue and influencing anti-tumor immunity in ovarian cancer. This breakthrough could reshape our future understanding of the microbiome’s role in cancer treatment and immune system modulation

Moreover, tumor immunology has transformed cancer treatment, with the development of immunotherapies offering hope for life-changing outcomes. The department’s groundbreaking research into the tumor-immune system interface is paving the way for future novel cancer treatments.

By focusing on emerging fields, leveraging cutting-edge technologies, and recruiting talented junior scientists, this department is poised to remain at the forefront of innovation and discovery for generations to come.