The University of Massachusetts Amherst

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M. Sloan Siegrist

Assistant Professor

The cell envelope is an essential interface between a bacterium and its surroundings. This dynamic structure accommodates the basic cellular processes of growth and division while protecting against environmental and immune insults. Because it is essential for viability and is composed in part of molecules that are not present in host cells, the bacterial cell envelope has been a particularly fruitful target for antibiotic development. Both the remarkable biology and medical potential of the cell envelope have inspired steady research on the topic for over half a century. Indeed, cell envelope synthesis and remodeling are well described for model bacteria replicating in broth culture. However, the vast majority of species are unlikely to fit this paradigm neatly. Moreover, these processes have been primarily studied under defined conditions that may or may not recapitulate the natural environment.

Current Research
Our research focuses on the cell envelope of intracellular pathogens such as Mycobacterium tuberculosis and Listeria monocytogenes. The broad goals of our lab are (1) to determine the mechanisms by which these pathogens adapt their cell envelope to the host environment and (2) to engineer the bacterial cell envelope for basic and translational biomedical applications. To tackle these challenges, we draw from multiple disciplines and develop new tools when appropriate.

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Academic Background

  • BA Human Biology, Stanford University
  • PhD Immunology and Infectious Diseases, Harvard School of Public Health
  • Postdoctoral training: Department of Chemistry, U.C. Berkeley
Brown A, Gordon R, Hyland S, Siegrist MS, Grimes CL (2020) “Chemical biology tools for examining the bacterial cell wall.” Cell Chemical Biology.
Koyasseril-YehiyaTM, García-Heredia A, Anson F, Rangadurai P, Siegrist MS , Thayumanavan T (accepted) “Supramolecular Antibiotics: A Strategy for Conversion of Broad-Spectrum to Narrow-Spectrum Antibiotics for Staphylococcus aureus.” Nanoscale.
García-Heredia A, Kado T, Sein CE, Puffal J, Osman SH, Judd J, Gray TA, Morita YS, Siegrist MS (2020) “The mycobacterial cell wall partitions the plasma membrane to organize its own synthesis.” bioRxiv 544338 [preprint].
Pohane AA, Moore DJ, Nathan TO, Gepford DM, Kavunja HW, Swarts BM, Siegrist MS (2020) “A cascading chemical reporter for in situanalysis of cell envelope recycling in mycobacteria
Kavunja HW, Biegas KJ, Banahene N, Stewart JA, Piligian BF, Groenevelt JM, Sein CE, Morita YS, Niederweis M, Siegrist MS, Swarts BM (2020) “Photoactivatable glycolipid probes for identifying mycolate-protein interactions in live mycobacteria.” JACS.
Rivera SL, Espaillat A, Aditham AK, Shieh P, Muriel-Mundo C, Kim J, Cava F, Siegrist MS (2019) “Bacterial Peptidoglycan Stapling with Functionalized d-Amino Acids” chemRxiv10248764 [preprint].
Fiolek TJ, Banahene N, Kavunja HW, Holmes NJ, Rylski AK, Pohane AA, Siegrist MS, Swarts BM (2018) “Engineering the Mycomembrane of Live Mycobacteria with an Expanded Set of Trehalose Monomycolate Analogues." ChemBioChem
Melzer ES, Sein CE, Chambers JJ, Siegrist MS (2018) “DivIVA concentrates mycobacterial cell envelope assembly for initiation and stabilization of polar growth.” Cytoskeleton (bioRxiv 341073).
García-Heredia A Pohane AA, Melzer ES, Carr CR, Fiolek TJ, Rundell SR, Lim HC, Wagner J, Morita YS, Swarts BM, Siegrist MS (2018) “Peptidoglycan precursor synthesis along the sidewall of pole-growing mycobacteria.” eLife (bioRxiv 292607). • Insight article in “Tuberculosis: Breaking down walls,” eLife • Spotlight article in “Building Walls: Work that Never Ends,” Trends in Microbiology • Finalist for Mahoney Life Sciences Prize
Puffal J, García-Heredia A, Rahlwes KC, Siegrist MS, Morita YS (2018) “Spatial control of cell envelope biosynthesis in mycobacteria.” Pathogens & Disease.
Hayashi JM, Richardson K, Melzer ES, Sandler SJ, Aldridge BB, Siegrist MS, Morita YS (2018) “Stress-induced Reorganization of Mycobacterial Membrane Domain.” mBio.
Fimlaid KA, Jensen O, Siegrist MS, Shen A (2015) “A conserved channel regulates multiple stages of Clostridium difficile spore morphogenesis.” PLoS Genetics.
Contact Info

Department of Microbiology
110 Morrill IV North
639 North Pleasant Street
Amherst, MA 01003-9292

(413) 545-2735