By Hubza Syeda, Postbac in the Molecular Immunoengineering Section, Viral Pathogenesis Laboratory (VPL), Vaccine Research Center (VRC) and Micah Young, Postbac in the Mosquito Immunity and Vector Competence Section, Laboratory of Malaria and Vector Research (LMVR), Division of Intramural Research (DIR)
The NIAID Postdoc Spotlight Series was held virtually in 2022 to provide NIAID postbacs with the opportunity to learn about the outstanding research conducted by NIAID Postdocs. The postdocs selected for these talks come from various research areas with the aim of highlighting the scope of NIAID research. This summer’s speakers included Ai Ing Lim, PhD., Sila Ataca, Ph.D., Kyle O’Donnell, Ph.D., and Guney Boso, Ph.D.
Pre-birth Immune Education
Ai Ing Lim, PhD. Postdoctoral fellow, Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome (LHIM), Division of Intramural Research (DIR)
Brief Summary of Dr. Ai Ing Lim’s research seminar
In an environment where we are constantly challenged with microbes, our immune system is the frontline that maintains balance between our body and the external world. These microbes play a fundamental role in shaping the development of the immune system. Dr. Lim’s research in the Metaorganism Immunity Section of the Laboratory of Host Immunity and Microbiome focuses on pre-birth immune education, specifically how maternal infection plays a role in the immune profile of offspring and, reciprocally, how maternal immunity changes to adapt to the physiological changes that occur during pregnancy and lactation. Dr. Lim shows that in pregnant mice infected with an attenuated foodborne pathogen, Yersinia pseudotuberculosis, offspring have elevated levels of T helper 17 cells in their intestine, and this is shown to be mediated by maternal interleukin-6 (IL-6). IL-6 was shown to impact the epithelial stem cells during fetal development, as the adult offspring were shown to have enhanced resistance to certain infections but were more susceptible to inflammation.
Key Takeaways
The experience of mothers during pregnancy provides a pre-birth immune education that prepares offspring for the world they are going to enter. As Dr. Lim says in her talk, "the immune system is highly plastic and can adapt to environmental challenges before birth."
Elicitation of broadly neutralizing antibodies recognizing the stem supersite of group 1 and group 2 influenza hemagglutinins in human VH1-69 knock-in mice
Sila Ataca, Ph.D. Postdoctoral fellow, Molecular Immunoengineering Section, Viral Pathogenesis Laboratory (VPL), Vaccine Research Center (VRC)
Brief Summary of Dr. Sila Ataca’s research seminar
Antigenic variation is a constant challenge in the development of a universal influenza vaccine. Dr. Ataca’s work in the Molecular Immunoengineering Section at the Vaccine Research Center focuses on characterizing the immune responses to influenza (flu) hemagglutinin (HA), a surface glycoprotein that is the focus of many vaccine efforts. While seasonal flu vaccines induce strain-specific immunity, universal flu vaccines aim to elicit broadly neutralizing antibodies which have the ability to bind to and block parts of the virus that are conserved across strains and from year to year. Broadly neutralizing antibodies can protect us against different types and subtypes of flu, such as both group 1 and group 2 influenza A viruses. Using an immunization strategy that consists of priming with a group 2 stem immunogen followed by two boosts with a group 1 stem immunogen can elicit cross-group reactive neutralizing and protective antibodies in a humanized mouse model. This additional group 2 specificity, they find, comes from utilizing the DH3-9 antibody gene segment to target the HA stem domain.
Key Takeaways
Beyond her science, Dr. Ataca shared some career advice. She noted that computational skills are essential no matter your scientific field, as data processing and analysis are frequently cited as one of the most valuable skillsets. She also recommended joining a collaborative lab that can benefit you in the long-term by providing more exposure to different people, ideas, and skillsets.
My Road to the NIH and What I’ve Done with My Time Here
Kyle O’Donnell, Ph.D. Postdoctoral fellow, Immunobiology and Molecular Virology Unit, Laboratory of Virology (LV), Division of Intramural Research (DIR) at the Rocky Mountain Laboratories (RML)
Brief Summary of Dr. Kyle O’Donnell’s research seminar
After spending much of his early career researching avian antibodies against viral pathogens, Dr. Kyle O’Donnell now works in the Immunobiology and Molecular Virology Unit at the Rocky Mountain Laboratories to develop novel vaccines against human viruses, such as SARS-CoV-2 and Marburg virus. He is currently investigating vesicular stomatitis virus (VSV) as a candidate for a live, attenuated vaccine. The advantages of VSV-based vaccines are that they are easy to manipulate genetically, they grow to high titers, prior immunity is uncommon, and they have a fast-acting time to immunity, making them excellent candidates for vaccines in humans. Dr. O’Donnell has utilized the VSV vaccine platform to design a live, attenuated vaccine against Marburg virus, for which there are no currently approved vaccines or therapeutics. He began work to optimize the vaccine so that more doses could be administered per vial of vaccine. Most recently, he has shown that a single dose as low as 103 PFU (from the original 107 PFU) resulted in 100% protection of nonhuman primates (NHPs) when administered 14 days prior to challenge. His data demonstrated that NHPs immunized with the vaccine maintained a mature and multi-functional antigen-specific antibody response for up to 42 days post vaccination. In the future, he will continue to characterize the cellular immune response.
Key Takeaways
Dr. O’Donnell is passionate about understanding the role natural killer cells play in VSV-based vaccine immunity and antiviral functions, as well as characterizing the humoral immune response beyond simple neutralization. Dr. O’Donnell spoke about the outstanding working relationship he has formed with his mentor, Dr. Andrea Marzi, and described how thankful he was for the training he received in the biosafety level-4 lab.
Paleovirology: Domestication of an Ancient Retroviral Gene in a Primate Lineage
Guney Boso, Ph.D. Postdoctoral Research fellow, Viral Biology Section, Laboratory of Molecular Microbiology (LMM), Division of Intramural Research (DIR)
Brief Summary of Dr. Guney Boso’s research seminar
Dr. Boso became interested in the evolution of host response to viral infections as he looked at host- immune proteins that interfere with HIV infection, leading him down a fascinating line of inquiry full of ancient retroviral genes that have been “domesticated” in their host. Dr. Boso, who now works in the Viral Biology Section of the Laboratory of Molecular Microbiology , explained that retroviral infections of the germline are extremely rare events that result in viral DNA being incorporated and passed down into the genome of the progeny of the infected individual. He further explained that many of these retroviral genes are mutated out over time, but some of these genes remain intact—and are actually beneficial. An interesting example of this is a group of proteins called “syncytins” that are remnants of retroviral envelope proteins domesticated in various mammals (including humans) and help create a special layer of cells in the placenta that allow the nutrient exchange between the mother and the fetus. Using these discoveries as a guide, Dr. Boso identified an intact retroviral gag gene—which codes for the structural proteins of the virus—in humans and other primates that is also expressed specifically in the placenta. He is now utilizing bioinformatic tools combined with molecular biology methods to find other ancient retroviruses that have been domesticated, are intact, and are being expressed in different mammal lineages. Dr. Boso mentioned that his “ultimate goal is to become a gene discoverer.”
Key Takeaways
Now that he is working on the co-evolution of retroviruses with their mammalian hosts, Dr. Boso hopes to identify ancient retrovirus genes whose function has been domesticated and utilized by the host for its own benefit. Dr. Boso hopes to contribute to the field of science either by working at universities where he can educate the next generation of scientists or by working as a scientific reviewer here at NIH.