Engineering Beneficial Bacteria to Improve Human Health

The human microbiome is a complex and dynamic ecosystem of microorganisms that live in and on the human body. These microorganisms, including bacteria and viruses, play a crucial role in maintaining health and preventing diseases. Though we are only just beginning to understand the many ways in which these microorganisms impact health, the advance of next generation genetic sequencing technologies has enabled us to reveal the composition of the human microbiome. Scientists are working to better understand the interactions between the microbiome and the human host, as well as potential ways to manipulate the microbiome to improve health. One of my long-term research goals as a Ph.D. student and FFAR Fellow at North Carolina State University is to develop human biotherapeutics that harness the power of the human microbiome to cure and treat diseases.

I develop genetic engineering tools, particularly CRISPR-based technologies, to modify and manipulate bacteria found in the human microbiome. I work primarily with two specific types of bacteria that are commonly found in the healthy gut: Lactobacillus and Bifidobacterium. These bacteria are important probiotics that are known to have a range of health benefits, including aiding in digestion, boosting the immune system and alleviating irritable bowel syndrome (IBS). I believe that we can genetically engineer and manipulate the microbiome with fine-tuned precision to greatly improve human health.

Engineering requires precision. One of the biggest hurdles in engineering the human microbiome is its sheer complexity. This dynamic ecosystem can be influenced by various factors including diet, medication and environmental exposures, not to mention the vast number of different microbes residing in this ecosystem. Given the expertise of our lab, led by Dr. Rodolphe Barrangou, we address a challenge that is directly related to the mechanics of genetically modifying Lactobacillus and Bifidobacterium: these bacteria only grow in environments where there is little or no oxygen, which makes working with them extremely tricky. Over the past few years, we successfully engineered Lactobacillus to serve as a vaccine delivery system against viral infections such as rotavirus and Covid-19. Since Lactobacillus is native to the human gut, it can bypass biological hurdles such as gastric acid which destroy non-native bacteria. The engineered Lactobacillus then replicates in the gut, stimulating the host immune system to create a long-lasting immune response that provides protection against future infection. We also developed CRISPR-based tools for genome engineering in Bifidobacterium. The study of Bifidobacterium genetics has been hampered by both intrinsic and extrinsic factors. Its thick cell wall prevents efficient transformation and the abundance of primary defense systems (such as restriction-modification systems) degrades foreign DNA once inside of the cell. The development of CRISPR tools in our study opens new avenues to engineer Bifidobacterium probiotics and to study their health-promoting effects in human health.

Being a FFAR fellow has been a valuable and rewarding experience for me. I have had the opportunity to connect with other brilliant FFAR fellows and professionals in the biotechnology industry and benefit from industry mentorship. This has provided valuable guidance and support for my career development. After graduation, I hope to join the biotechnology industry and use my expertise in molecular biology to develop innovative therapies that can have a meaningful impact on human health. I am excited to be a part of this rapidly advancing field and to contribute to the understanding of the human microbiome and its role in health.