
Tami Lieberman, associate professor, Department of Civil and Environmental Engineering, and a core faculty member of IMES, describes how her research developing tools, theories, and conceptual models will facilitate the next generation of microbiome therapeutics for the skin.
Mindy Blodgett | IMES
Tami Lieberman trained in molecular biology and mathematics at Northwestern University, where she conducted research in the laboratory of Jon Widom and was funded by a Barry M. Goldwater Scholarship. She then earned a PhD in Systems Biology from Harvard University, joining the MIT faculty in 2018. She now leads a computational and experimental research group, the Lieberman Lab, which is focused on within-person evolution in the skin microbiome, leveraging evolutionary inference to learn the recent natural history of bacterial strains within complex communities to build principles for precisely engineering microbiomes. Using human skin as the primary model ecosystem, Lieberman's research focuses on computational tools, unique sample collections, and statistical approaches to address questions poorly understood for any microbial community.
Research in the Lieberman Lab centers around within-person evolution, with projects spanning from theoretical population genetics to applied probiotics for the treatment of skin diseases. Can you tell us more about how researching evolution within human skin microbiome has the potential to unlock treatments for various diseases, and to advance human health?
The potential for rationally designed probiotics for the gut, skin, and other body sites is vast. Scientists are uncovering naturally occurring and designed probiotics that might one day be taken to outcompete bacteria that contribute to inflammatory bowel disease or atopic dermatitis, regulate the immune system, or deliver a payload to a specific body site. Long-lived engineered probiotics might one day replace costly routinely applied products like moisturizers, vitamins, and sunscreen, lowering the risk of future disease with a lower carbon footprint.
However, we still remain severely limited in our ability to precisely manipulate microbiomes and most topically applied probiotics simply do not stick. We do not know how to predict if a given species or strain of bacteria will stably colonize an individual. This unpredictability in strain establishment highlights the fact that we need to know more about the ecology and evolutionary landscape of microbiomes to realize the great potential of the microbiome therapeutics.
My lab primarily studies the skin microbiome, which enables easy access to microbes in the location that they live. Understanding the spatial organization of communities is critical for understanding why microbes can or cannot coexist and how the evolve. For example, we have discovered that the most predominant species on skin—Cutibacterium— resides in nearly genetically identical populations in individual facial pores, despite each person having a wide range of diversity of this species on the skin surface. We went on to show that the physical structure of the pore creates a bottleneck that limits within-pore diversity. This has helped us understand why so many different types of C. acnes are found on each person—they simply don’t compete that much with one another. Moreover, it tells us that any probiotic C. acnes strain development (and folks are working on C. acnes probiotics)doesn’t need to focus on picking the right strain and instead should focusing on removing strains already resident in pores (e.g. by deep cleansing).
More recently, my lab has revealed that C. acnes probiotics are the most likely to successfully establish during a teen’s transition to an adult skin microbiome, when excess oil production enables an increase in population size on the face and therefore eases the colonization process. In the same study, we showed that the next most abundant bacteria on skin, S. epidermidis, is unlikely to ever be a long-lasting probiotic species, as there is high turnover at the strain level constantly throughout life.
These translational insights, which were inaccessible using classical microbiome techniques, were made by tracking these bacteria at the whole genome level and using the mutations they accumulate during evolution to understand their past dynamics—in much the way that SARS-CoV2 mutations were used in the early days of the pandemic to understand the multi-origin nature of spread in the USA. We also use the mutations the bacteria accumulate themselves to understand what the bacteria care about in vivo. Among other findings, we have shown that Staphylococcus aureus frequently loses its protective capsule on eczematic skin, and that Staphylococcus epidermidis needs to survive antibiotics produced by other members of the same species (intraspecies warfare!) to thrive on normal skin. These findings can help us develop strategies to thwart the growth of less desired bacteria, promote the growth of beneficial strains in the skin, and develop similar translational insights in the gut and other less easily accessible microbiomes.
In addition to being a core faculty member of IMES, you are a part of the Department of Civil and Environmental Engineering (CEE). You are also a member of the Center for Microbiome Informatics and Therapeutics (CMIT), an affiliate member at the Broad Institute and an associate member of the Ragon Institute. How have these cross-disciplinary connections within MIT and connections with the medical community in the greater Boston impacted your work?
Our connections to other microbial ecologists within CEE provide a strong foundational science network for my group. Our close connection with these colleagues has helped me recruit amazing scientists interested in fundamental basic science questions, as these individuals know they will be surrounded by other experts in ecology, genomic sequencing, and environmental sensing. CMIT and the broader medical community in the Boston area have catalyzed multiple new translational areas of research in my lab—including the above-mentioned discovery of adaptation on eczematic skin (facilitated through CMIT) and the study of the microbiome of normally healing skin wounds, which has led to a pending patent application. These physician collaborators not only help us access patients, but ensure clinical relevance to the questions we ask. In addition, the great wealth of speakers brought to the Boston area through CMIT has led to new collaborations, including on the facial skin microbiome of chimpanzees and gorillas.
Can you tell us a bit about your background, and about how it is that you became interested in studying human skin to better understand microbial dynamics? What are your goals for your research, and for your career?
During my PhD, I studied real-time evolution of bacteria during long term infections. Whole genome sequencing had finally gotten affordable enough to sequence multiple bacterial colonies from the same infection or outbreak, and I was lucky enough to be involved in landmark studies tracking within-person evolution within and across people. We wound up focusing on a rare bacterial species, Burkholderia dolosa, that caused an outbreak among people with the inherited disease cystic fibrosis in the Boston area. In the course of just a couple of years, we were able to understand how this bacteria spreads across people, across organs, and identify which genes it sees as most important to change in vivo— without knowing what these genes did beforehand or having developed this rare species into a ‘model system’ in the lab.
At the same time, the microbiome field was growing as a result of the Human Microbiome Project (HMP) funded by the NIH. These studies were showing that there were hundreds or thousands of new species residing on humans that would need to be studied, and there wouldn’t be enough labs in the world to study them one-by-one. We needed methods to rapidly gain insights into which genes needed to be understood, how these organisms spread, and to tell us which genes to focus on for each species—and I figured the lens of whole genome evolution could help. I joined Eric Alm’s lab to apply these techniques to the gut microbiome, and then decided to focus primarily on skin when I started in 2018. Facial skin microbiome is more tractable than the gut microbiome because: (1) we can sample microbes from where they live; (2) it has relatively fewer species, enabling us to study species individually and their interaction; and (3) it has a relatively universal composition across all healthy humans studied to date—which should make it easier to engineer.
Going forward, my lab aims to uncover rules of microbial colonization that will facilitate the next generation of microbiome therapeutics for the skin. We will also seek to understand the role of microbiome in disease, including revisiting the role of microbes in acne vulgaris. At the same time, we will continue to develop tools, theories, and conceptual models that will accelerate all microbiome research more generally. We aim to be able to predict how natural and applied bacterial strains will navigate the complex and shifting ecological landscapes on and inside each of us.