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Northwestern University Feinberg School of Medicine
Research

Mark Mandel, PhD Assistant Professor of Microbiology-Immunology

Mark Mandel, PhD

Mark Mandel, PhD, assistant professor in the Department of Microbiology-Immunology, grew up outside of Buffalo, New York. He studied biology at Cornell University in Ithaca, New York, and conducted his PhD training in Thomas Silhavy’s lab at Princeton University, where he focused on starvation signal transduction in Escherichia coli. In 2005, he moved to Madison, Wisconsin, to begin his postdoctoral fellowship with Ned Ruby at the University of Wisconsin. He joined Feinberg in 2010 as an assistant professor.

In his free time, Mandel enjoys spending time with his wife and two-year-old daughter visiting many Chicago-area museums. Some of their current favorites include the Shedd Aquarium, the Field Museum, and the Museum of Science and industry. Mandel also enjoys golfing and music at Millennium Park.

Q: What brought you to Feinberg?
A: Strong commitments to quality science and graduate student training within the microbiology-immunology department were very important factors. There is a wide range of expertise and experience within the department and an environment that emphasizes mentorship. As a new faculty member, it was especially appealing to join a group in which faculty are taking risks to make more significant scientific contributions. As I begin my research program, the advice and assistance that my lab is receiving from our neighbors is allowing us to quickly get set up and address important questions.

Q: What are your research interests?
A: Although many animals form reproducible relationships with microbes, they are often born sterile and have to harvest their resident microbes (“microbiota”) from the environment. The manner by which animal-microbe communication leads to specificity during partner choice is not understood. I am interested in how this process occurs on a fundamental level: How does the host recognize its cognate microbe(s)? How does the microbe enter the host properly? How does the host know to accept the mutualist and not reject it as a pathogen? How is a long-term, chronic, beneficial association maintained? How does the daily signaling between host and microbe facilitate the beneficial interaction? How does the specificity between host and microbe thwart non-specific cheaters?

To answer these questions, we focus on a model symbiosis between the luminous marine Gram-negative bacterium Vibrio fischeri and its host Euprymna scolopes, the Hawaiian bobtail squid. V. fischeri is the only symbiont in the squid’s light organ.

The light produced by the bacteria camouflages the shadow generated by the near-shore swimming squid, thereby protecting the host from predation. We collect adult squid from Hawaii twice each year. They lay thousands of eggs in the lab and the juvenile squid that hatch lack symbionts that can be colonized with culture-grown bacteria (GFP-labeled, mutants, mutant libraries, etc.). By isolating a system in which there is one symbiont and one host, and by studying the association in the intact animal—including the full innate immune system of the host—we are identifying conserved principles underlying host association by microbes.

With this model, we are using forward genetics and genome-scale approaches to identify and characterize relevant bacterial factors that mediate host interaction and specificity.

Q: How did you become interested in this?
A: As an undergraduate, I was in a laboratory in which each member studied a different natural system. As a result, I came to appreciate the benefits of conducting molecular biology that was closely tied to nature. As a graduate student, I realized how the power of bacterial genetics facilitated detailed mechanistic studies. I enjoyed both ends of the spectrum and the prospect of determining detailed mechanisms that could then be related back to ecology and evolution.

I was also convinced that by conducting experiments on natural isolates we could determine biology that would not be possible in more laboratory-adapted systems. For my long-term research on the symbiosis between squid and V. fischeri, I looked for a system in which these two interests could be merged, and in that sense it has worked out very well. When we identified a gene that was sufficient to alter the host range of the bacterium, we were able to immediately relate the functional data in the laboratory to changes in patterns of host colonization observed in nature.

Q: What papers have you recently published and where?
A: Mandel MJ. 2010. Models and Approaches to Dissect Host-Symbiont Specificity. Trends Microbiol 18:504-511.

Wier AM, Nyholm SV, Mandel MJ, et al. 2010. Transcriptional Patterns in both Host and Bacterium Underlie a Daily Rhythm of Ultrastructural and Metabolic Change in a Beneficial Symbiosis. Proc Natl Acad Sci USA 107:2259-2264.

Mandel MJ, Wollenberg MS, Stabb EV, Visick KL, Ruby EG. 2009. A Single Regulatory Gene is Sufficient to Alter Bacterial Host Range. Nature 458:215-218.

Q: What types of collaborations are you engaged in across campus (and beyond)?
A: We are part of a six-laboratory team that is building and characterizing a mutant library collection of V. fischeri strain ES114, the best-studied squid symbiont, which is organized by Cheryl Whistler at the University of New Hampshire.

For our genomics work (both genome sequencing and functional screening involving mutant populations), we have active collaborations with David Rasko at the Institute for Genome Sciences at the University of Maryland, and with Andrew Goodman at Yale University.

Although I just arrived at Northwestern last year, I am eager to develop more collaborations locally, especially with regard to computational biology approaches as we generate more and more data through next-generation sequencing.

Q: How does your research advance medical science and knowledge?
A: In the last five to 10 years, there has been an increased awareness that the human microbiota play important roles in immune development and homeostasis, epithelial development and nutritional homeostasis.

Humans are born sterile and must acquire the correct microbes for normal development. Altered microbiota have been associated with diseases such as inflammatory bowel disease, diabetes, obesity, and cancer.

Work in human subjects is defining the patterns of microbial colonization in humans at the phylum and species level. However, we do not understand the fundamental principles that govern how animals form specific relationships with the correct cognate microbes. To understand these processes, we turn to a model system that facilitates dissection of the animal-bacterial communication. This system allows for high-resolution bacterial genetics, imaging of the live infection and genomic approaches in the host and symbiont.



Q: How does your research advance medical science and knowledge?
A: In the last five to 10 years, there has been an increased awareness that the human microbiota play important roles in immune development and homeostasis, epithelial development and nutritional homeostasis.

Humans are born sterile and must acquire the correct microbes for normal development. Altered microbiota have been associated with diseases such as inflammatory bowel disease, diabetes, obesity, and cancer.

Work in human subjects is defining the patterns of microbial colonization in humans at the phylum and species level. However, we do not understand the fundamental principles that govern how animals form specific relationships with the correct cognate microbes. To understand these processes, we turn to a model system that facilitates dissection of the animal-bacterial communication. This system allows for high-resolution bacterial genetics, imaging of the live infection and genomic approaches in the host and symbiont.