Lee Kroos photo
Lee R. Kroos
Professor
Associate Chair
  • B.S. 1981, Bowling Green State University
  • Ph.D. 1986, Stanford University
  • NSF Predoctoral Fellow, 1981-84, Stanford University
  • Helen Hay Whitney Postdoctoral Fellow, 1986-88, Harvard University

kroos@msu.edu
422 Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-355-9726
Lab: 517-353-0809
FAX: 517-353-9334

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Lee Kroos Research Interests

Certain bacteria undergo developmental processes that include cell fate determination, cell to cell signaling, morphogenesis, and cellular differentiation. We exploit the biochemical and genetic simplicity of bacteria to explore the molecular mechanisms of gene regulation and protein function during development. The novel mechanisms we discover are likely to be used by many other microorganisms of medical, agricultural, and environmental importance.

Bacillus subtilis is a soil bacterium that undergoes development when starved. The cell is partitioned into two compartments, the mother cell and the forespore, each of which expresses distinct sets of genes in an ordered temporal fashion, under the control of different sigma subunits of RNA polymerase (Fig. 1).

We are investigating the regulation of genes that are expressed in the mother cell compartment during the later stages of sporulation under the control of sK RNA polymerase. We have shown that sK is first made as an inactive precursor (pro-sK) and that processing to the active form in the mother cell depends on a signal from the forespore. Our current model for this novel type of signal transduction pathway is shown in (Fig. 2).

SpoIVFB appears to be the protease that processes pro-sK. It is a member of a new family of putative metalloproteases that are believed to cleave their substrates within or adjacent to membranes. Although homologs are present in nearly all organisms studied, including humans, very little is known about their function. Our aims are to establish the function of SpoIVFB, to understand its regulation by a signal from the forespore, and to elucidate the requirements for pro-sK to serve as a substrate for processing.

Once active sK is made, it activates late genes in the mother cell, and expression of early genes is inhibited by several mechanisms (Fig. 3). What are the molecular mechanisms involved in the switch from early to late gene expression and how important is each in the sporulation process? One important component of the switch is SpoIIID, a DNA-binding protein that activates or represses transcription of many different mother cell-specific genes. We want to understand how SpoIIID activates transcription of essential early genes like sigK (encoding pro-sK) and whether its repression of late cot genes (encoding spore coat proteins) is important for sporulation.

Myxococcus xanthus is a soil bacterium that undergoes a multicellular developmental process requiring several cell-cell signals (Fig. 4). C-signaling regulates motility and differentiation of starved M. xanthus, resulting in aggregation followed by sporulation within a fruiting body. C-signaling also regulates the expression of nearly all genes induced after the early aggregate stage. Some components of the C-signal transduction pathway are known (Fig. 5). Our lab has characterized the regulatory regions of genes that depend on C-signaling for expression. Ongoing studies include mutational analyses of promoter regions to identify cis -acting DNA elements and a variety of approaches to identify trans -acting transcription factors. Our goal is to understand how C-signaling regulates genes temporally and spatially during M. xanthus development.

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