BBS Faculty Member - David Rudner

David Rudner

Department of Microbiology

Harvard Medical School
Microbiology, HIM, room 1025
77 Ave Louis Pasteur
Boston, MA 02115
Tel: 617-432-4455
Fax: 617-738-7664
Email: rudner@hms.harvard.edu
Visit my lab page here.



Work in the Rudner lab focuses on fundamental questions in bacterial cell biology and development: How do bacteria enter and exit dormancy? How are replicated chromosomes organized and segregated? How is the cell envelope remodeled during growth and differentiation? And how do cells sense and respond to problems that arise during the construction of the envelope? We address these questions in the model gram-positive bacterium Bacillus subtilis, in many cases, taking advantage of the developmental process of spore formation in this organism.

In response to starvation, B. subtilis differentiates into a metabolically inactive spore that can resist extreme environmental insults including antibiotics. Spores can remain dormant (and stress resistant) for decades yet upon exposure to nutrients can germinate and resume growth within minutes. The genes required to exit from dormancy are known but how their protein products work and how they work together remain mysterious. We are interested in defining the germination pathway in molecular detail with a long-term goal of identifying small molecule agonists and antagonists of germination.

Spore-formation in B. subtilis is one of the most well characterized differentiation processes in biology. Virtually every step in the process has been defined in molecular detail. With this knowledge in hand, we are now investigating how other bacteria differentiate into dormant spores. We are using high-throughput genetic approaches to define the complete set of sporulation genes in spore-forming pathogens to identify the similarities and differences in how these bacteria enter and exit dormancy. Our long-term plans are to molecularly characterize novel sporulation genes and pathways in these organisms.

Growth, division, and morphogenesis involve a highly choreographed interplay between synthesis and degradation of the cell wall peptidoglycan. This macromolecule is composed of glycan strands crosslinked to one another by short peptides to form a three-dimensional meshwork that encapsulates the cytoplasmic membrane, provides cell shape, and protects the cell from osmotic rupture. Some of our most enduring antibiotics target the synthesis of this essential exoskeleton. We are interested in how bacteria build and remodel their envelope layers during growth and how they sense and respond to problems that arise during its construction. A deeper understanding of these processes has the potential to define new targets for antibiotic development. We are currently focused on dissecting stress-response pathways that monitor the synthesis of the cell wall and modulate gene expression to ensure the cell maintains envelope homeostasis.

How chromosomes are replicated, organized, and segregated are outstanding questions in all organisms. We study these processes during growth and differentiation in B. subtilis. Our research has principally focused on three of the most highly conserved factors in bacterial chromosome organization and segregation: the parABS partitioning locus, the SMC condensin complex, and the SpoIIIE/FstK DNA translocase. We are also engaged in cytological and classical genetic screens to identify novel factors that influence the organization and segregation of the B. subtilis chromosome.



Last Update: 8/19/2019



Publications

For a complete listing of publications click here.

 


 

Ramírez-Guadiana FH, Rodrigues CDA, Marquis KA, Campo N, Barajas-Ornelas RDC, Brock K, Marks DS, Kruse AC, Rudner DZ, (2018) Evidence that regulation of intramembrane proteolysis is mediated by substrate gating during sporulation in Bacillus subtilis. PLoS Genet. 14(11):e1007753.

Ramírez-Guadiana FH, Meeske AJ, Rodrigues CDA, Barajas-Ornelas RDC, Kruse AC, Rudner DZ, (2017) A two-step transport pathway allows the mother cell to nurture the developing spore in Bacillus subtilis. PLoS Genet. 13(9):e1007015.

Wang X, Brandão HB, Le TB, Laub MT, Rudner DZ, (2017) Bacillus subtilis SMC complexes juxtapose chromosome arms as they travel from origin to terminus. Science 355:524-527. 

Meeske AJ, Riley EP, Robins WP, Uehara T, Mekalanos JJ, Kahne D, Walker S, Kruse AC, Bernhardt TG, Rudner DZ, (2016) SEDS proteins are a widespread family of bacterial cell wall polymerases. Nature 537:634-638. 

Meeske AJ, Rodrigues CD, Brady J, Lim HC, Bernhardt TG, Rudner DZ, (2016) High-Throughput Genetic Screens Identify a Large and Diverse Collection of New Sporulation Genes in Bacillus subtilis. PLoS Biol. 14(1):e1002341.



© 2016 President and Fellows
of Harvard College