Department of Cellular and Molecular Medicine
Jan Claesen, PhD
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 636-3246
Fax: (216) 444-9404
The Claesen group aims to functionally characterize molecular mechanisms that control bacterial interspecies and microbe-host interactions in the human microbiome. Bacteria use small molecule chemicals to mediate these interactions and the genetic information required for their production is typically encoded in one physical location of the bacterial chromosome, in biosynthetic gene clusters (BGCs). Using in silico techniques, we identified several widespread families of BGCs that we are now characterizing experimentally, prioritizing on the BGCs predicted to be involved in modulation of community composition or interaction with the host immune system. Our research will contribute to a better mechanistic understanding of the microbes that live in our gut, leading to the discovery of druggable small molecules, new targets for antibacterial therapy and beneficial bacterial strains that can be employed for intervention therapies. The areas of expertise in the Claesen group include microbiology, bacterial genetics and synthetic biology, small molecule biosynthesis and biochemistry.
In other words ...
Thanks to the Human Microbiome Project, we know what bacteria are living at various locations on and inside a healthy human body. This research led to the surprising discovery that there are far more different kinds of bacteria present and at much higher numbers than was previously thought. Most of these bacteria are harmless, “good” organisms with the largest number living in the intestinal tract. They are essential to human health and life as they contribute to digesting food, providing essential nutrients and vitamins, and ensuring the effective operation of the immune system to prevent infection by disease-causing, “bad” bacteria. In fact, many recent studies have linked diseases of the digestive tract, including obesity, type 2 diabetes, inflammatory bowel diseases and certain colon cancers, to an imbalance in the bacterial community. It is therefore of great importance to understand how the right balance of microbes and their function is maintained in a healthy intestinal tract.
Where the Human Microbiome Project answered the initial question of “Who is there?”, we at the Claesen group focus on tackling the logical follow-up question “What are they doing?”. We discovered different classes of small molecules produced by “good”, commensal microbes that are used for communicating with other bacteria as well as with the host immune system. We predict that these are used in lively, molecular conversations that are essential for maintaining a healthy intestinal tract. Our research will yield a better understanding of the role the microbiome plays in disease, as well as drive the development of microbiota-based therapies.
9. Smanski MJ, H Zhou, J Claesen, B Shen, MA Fischbach, and CA Voigt (2016). Synthetic biology to access and expand nature's chemical diversity. Nat Rev Microbiol, 14(3): 135-149.
8. Thanapipatsiri A, J Claesen, JP Gomez-Escribano, M Bibb, and A Thamchaipenet (2015). A Streptomyces coelicolor host for the heterologous expression of Type III polyketide synthase genes. Microb Cell Fact, 14(1): 145.
7. Medema MH, R Kottmann, P Yilmaz, M Cummings, JB Biggins, K Blin, I de Bruijn, YH Chooi, J Claesen, RC Coates, et al. (2015). Minimum information about a biosynthetic gene cluster. Nat Chem Biol, 11(9): 625-631.
6. Claesen J, and MA Fischbach (2015). Synthetic microbes as drug delivery systems. ACS Synth Biol, 4(4): 358-364.
5. Wollenberg MS*, J Claesen*, IF Escapa, KL Aldridge, MA Fischbach, and KP Lemon (2014). Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus aggregation and biofilm formation. mBio, 5(4): e01286-01214. (*equal contribution)
4. Cimermancic P*, MH Medema*, J Claesen*, K Kurita, LC Wieland Brown, K Mavrommatis, A Pati, PA Godfrey, M Koehrsen, J Clardy, BW Birren, E Takano, A Sali, RG Linington, and MA Fischbach (2014). Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell, 158(2): 412-421. (*equal contribution)
3. Claesen J, and MJ Bibb (2011). Biosynthesis and regulation of grisemycin, a new member of the linaridin family of ribosomally synthesized peptides produced by Streptomyces griseus IFO 13350.
J Bacteriol, 193(10): 2510-2516.
2. Claesen J, and M Bibb (2010). Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc Natl Acad Sci USA, 107(37): 16297-16302.
1. Goto Y, B Li, J Claesen, Y Shi, MJ Bibb, and WA van der Donk (2010). Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. PLoS Biol, 8(3): e1000339.