Grace Spatafora
Office
Old Chapel 205
Tel
(802) 443-5431
Email
spatafor@middlebury.edu
Office Hours
Spring 2024: Tuesdays from 10:00am until noon in MBH354 (and by appointment)

Streptococcus mutans is the principal causative agent of dental caries in humans. A major research objective in the Spatafora laboratory centers on identifying genes belonging to the S. mutans SloR metalloregulome and defining their potential involvement in the caries-forming process.

Homologs of the SloR metalloregulator in other pathogenic bacteria are known to modulate gene expression upon binding DNA in the presence of a metal ion co-repressor. We propose that SloR, in response to metal ion availability in the human oral cavity, modulates metal ion transport and virulence gene expression in such as way as to promote S. mutans persistence and pathogenesis in dental plaque. The results of microarray and real-time qRT-PCR experiments revealed SloR as a pleiotropic global regulator in S. mutans. Our work is presently focused on a subset of S. mutans virulence genes that we identified are subject to both manganese and SloR control and that are preceded by a SloR recognition element (SRE) that binds the metalloregulator. One of our research goals is to explore and compare the mechanisms by which SloR regulates S. mutans gene expression and so reveal the complexities of SloR metalloregulation in this important oral pathogen. We also plan to reveal the constituency and structural organization of the SREs that precede SloR-regulated virulence genes in S. mutans, and to investigate the structure of the purified SloR protein so that the details of the SloR:SRE interaction under conditions of physiological relevance to the plaque environment can be elucidated. Taken together, we propose that manganese-dependent SloR binding to specific palindromic SREs facilitates S. mutans virulence gene expression and cariogenesis. This research is important not only because it will advance our understanding of S. mutans gene regulation but also because it will reveal a basis for designing novel therapeutic agents that can target SloR-modulated virulence gene expression and so alleviate the S. mutans-induced cariogenic process.

Courses Taught

Course Description

Cell Biology and Genetics
In this introduction to modern cellular, genetic, and molecular biology we will explore life science concepts with an emphasis on their integral nature and evolutionary relationships. Topics covered will include cell membrane structure and function, metabolism, cell motility and division, genome structure and replication, the regulation of gene expression and protein production, genotype to phenotype relationship, and basic principles of inheritance. Major concepts will be illustrated using a broad range of examples from plants, animals, and microorganisms. Current topics in biology will be integrated into the course as they arise. 3 hrs. lect./3 hrs. lab

Terms Taught

Fall 2022, Spring 2024, Fall 2024

Requirements

DED, SCI

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Course Description

Immunology
In this course we will explore the human immune system and how it works to protect the body from infection. Students will be introduced to the cells and molecules of the immune system and how they work together to protect the host from foreign invaders. We will focus on the cellular and molecular mechanisms of innate immunity before exploring the cellular and genetic principles that underlie the adaptive immune response. Finally, we will investigate how innate and adaptive immunity work together to combat infection and how disease can arise from inadequacies in this coordinated host response. (BIOL 0145)

Terms Taught

Spring 2022, Fall 2023

Requirements

SCI

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Course Description

Independent Study
In this course students complete individual projects involving laboratory and/or field research or extensive library study on a topic chosen by the student and a faculty advisor. Prior to registering for BIOL 0500, a student must have discussed and agreed upon a project topic with a member of the Biology Department faculty. Additional requirements include attendance at all Biology Department seminars and participation in any scheduled meetings with disciplinary sub-groups and lab groups. This course is not open to seniors; seniors should enroll in BIOL 0700, Senior Independent Study. (BIOL 0211. Approval required) 3 hrs. disc.

Terms Taught

Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023, Fall 2023, Winter 2024, Spring 2024, Fall 2024, Winter 2025, Spring 2025

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Course Description

Senior Independent Study
In this course students complete individual projects involving laboratory and/or field research or extensive library study on a topic chosen by the student and a faculty advisor. Prior to registering for BIOL 0700, a student must have discussed and agreed upon a project topic with a member of the Biology Department faculty. Additional requirements include attendance at all Biology Department seminars and participation in any scheduled meetings with disciplinary sub-groups and lab groups. (BIOL 0211. Approval required; open only to seniors) 3 hrs. disc.

Terms Taught

Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023, Fall 2023, Winter 2024, Spring 2024, Fall 2024, Winter 2025, Spring 2025

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Course Description

Senior Thesis
Seniors majoring in Biology who have completed one or more semesters of BIOL 0500 or BIOL 0700 and who plan to complete a thesis should register for BIOL 0701. In this course students will produce a written thesis, deliver a public presentation of the research on which it is based, and present an oral defense of the thesis before a committee of at least three faculty members. Additional requirements include attendance at all Biology Department seminars and participation in any scheduled meetings with disciplinary sub-groups and lab groups. Open to Biology and joint Biology/Environmental Studies majors. (BIOL 0211 and BIOL 0500 or BIOL 0700 or waiver; instructor approval required for all students) 3 hrs. disc

Terms Taught

Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023, Fall 2023, Winter 2024, Spring 2024, Fall 2024, Winter 2025, Spring 2025

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Course Description

Independent Research
This course is for non-seniors wishing to conduct independent research in Molecular Biology and Biochemistry under the guidance of a faculty mentor. Additional requirements include attendance at all MBBC-sponsored seminars and seminars sponsored by the faculty mentor’s department, and participation in any scheduled meetings and disciplinary sub-groups and lab groups. (Approval required).

Terms Taught

Fall 2022, Fall 2023, Fall 2024

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Course Description

Senior Independent Research
Seniors conducting independent research in Molecular Biology and Biochemistry under the guidance of a faculty mentor should register for MBBC 0700 unless they are completing a thesis project (in which case they should register for MBBC 0701). Additional requirements include attendance at all MBBC-sponsored seminars and seminars sponsored by the faculty mentor’s department, and participation in any scheduled meetings and disciplinary sub-groups and lab groups. (Approval required).

Terms Taught

Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023, Fall 2023, Winter 2024, Spring 2024, Fall 2024, Winter 2025, Spring 2025

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Course Description

Senior Thesis
This course is for seniors completing independent thesis research in Molecular Biology and Biochemistry that was initiated in BIOL 0500, CHEM 0400, MBBC 0500, or MBBC 0700. Students will attend weekly meetings with their designated research group and engage in one-on-one meetings with their research mentor to foster understanding in their specialized research area. Students will also practice the stylistic and technical aspects of scientific writing needed to write their thesis. (BIOL 0500, CHEM 0400, MBBC 0500, MBBC 0700) (Approval required).

Terms Taught

Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023, Fall 2023, Winter 2024, Spring 2024, Fall 2024, Winter 2025, Spring 2025

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Publications

Select Publications:

*Indicates a Middlebury College student

Spatafora, G.,  Li, Y., He, X., Cowan, A., and Tanner, A.  2023 (under review).  The Evolving Microbiome of Dental Caries Microorganisms (Special Issue: Microbiome in Infectious Diseases).  

​Drummond, I., DePaolo, A., Kreiger, M., Driscoll, H., Ekstrom, K., and Spatafora, G. 2023.  Small regulatory RNAs are mediators of the Streptococcus mutans SloR regulonJ. Bacteriol. 205(9): e0017-23.  doi: 10.1128/jb.00172-23.  

Ruxin, T.R., Schwartman, J.A., Davidowitz, C.R., Peters, Z., Holtz, A., Haney, R.A. and Spatafora, G.A. 2021.  Regulatory involvement of the PerR and SloR metalloregulators in the Streptococcus mutans oxidative stress response.  J. Bacteriol. 203 (11).  doi: 10.1128/JB.00678-20

O’Brien, J.*, A. Pastora,*, A. Stoner* and G. Spatafora.  2020.  The S. mutans mntE gene encodes a manganese efflux transporter.  Mol. Oral Microbiol. 35 (3): 129-140.  https://doi.org/10.1111/omi.12286

Kajfasz, J., C. Katrak, T. Ganguly, J. Vargas, L. Wright*, Z. Peters*, G. Spatafora,  Abranches, J. and Lemos, J.  2020.  Mangnaese uptake, mediated by SloABC and MntH, is essential for the fitness of Streptococcus mutansmSphere  5:300764. (featured article, “editor’s pick”).

Monette, P.*, R. Brach*, A. Cowan*, R. Winters*, J. Weisman, F. Seybert, K. Goguen*, J. Chen, A. Glasfeld, and G. Spatafora.  2018.  Autoregulation of the Streptococcus mutans SloR metalloregulator is constitutive and driven by an independent promoter.  J. Bacteriol. June 2018, 200 (14) e00214-18; DOI:10.1128/JB.00214-18 (spot-lighted article).

Wenderska, I.B., A. Latos, B. Pruitt*, S. Palmer, G. Spatafora, D.B. Senadheera, and D.G. Cvitkovitch. 2016. Transcriptional profiling of the oral pathogen Streptococcus mutans in response to competence signaling peptide XIP. mSystems 2:e00102-16.

Crepps, S.C.*, E.E. Fields*, D. Galan*, J.P. Corbett*, E.R. Von Hasseln* and G. Spatafora. 2016. The SloR metalloregulator is involved in the Streptococcus mutans oxidative stress response.  Mol. Oral Microbiol. DOI:10.1111/omi.12147 (epub ahead of print).

Spatafora, G., J. Corbett*, L. Cornacchione*, W. Daly*, D. Galan*, M. Wysota*, P. Tivnan*, J. Collins*, D. Nye, T. Levitz, W.A. Breyer, and A. Glasfeld. 2015.  Interactions of the metalloregulatory protein SloR from Streptococcus mutans with its metal ion effectors and DNA binding site.  J. Bacteriol. 197:3601-3615 (spotlighted article). 

Downey, J.S., L. Mashburn-Warren, E. A. Ayala, D.B. Senadheera, W.K. Hendrickson*, L.W. McCall*, J.A. Godfrey*, D. C. Cvitkovitch, G. Spatafora#, and S.D. Goodman. 2014. In vitro manganese-dependent cross-talk between Streptococcus mutans VicK and GcrR: implications for overlapping stress response pathways. PLoSOne. doi:10.1371/journal.pone.0115975 (#co-corresponding author with S.D. Goodman). 

Merchant, A.* and G. Spatafora.  2014.  A role for the DtxcR familhy of metalloregulators in gram positive pathogenesis.  Molec. Oral Microbiol. 29:1-10.

Haswell, J.R.*, B.W. Pruitt*, L.P. Cornacchione*, C.L. Coe*, E.G. Smith* and G. Spatafora. 2013.  Characterization of the functioinal domains of the SloR metalloregulatory protein in Streptococcus mutansJ. Bacteriol. 195:126-134

Smith, E.G.* and G. Spatafora. 2012. Gene Regulation in Streptococcus mutans: Complex Control in a Complex Environment. J. Dent. Res. (featured as a Critical     Review in Oral Biology and Medicine) 91(2):133-141.

O’Rourke, K.P.*, J.D. Shaw*, M.W. Pesesky*, B.T. Cook*, S.M. Roberts*, J.P. Bond and G.A. Spatafora. 2010. Genome-wide characterization of the SloR metalloregulome in Streptococcus mutans. J. Bacteriol. 192:1433-43.

Levine, R.B.*, M.S. Constanza-Robinson and G. Spatafora. 2010.  Neochloris oleoabundans grown on anaerobically digested dairy manure for concomitant nutrient removal and biodiesel feedstock production. Biomass and Bioenergy, 35:40-49

Dunning, D.W.*, L.W. McCall*, W.F. Powell*, W. T. Arscott*, E. M. McConocha*, S. D. Goodman, and G. Spatafora. 2008. SloR modulatioin of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary. Microbiology 154:1132-43.

Rolerson, E*, A. Swick*, L. Newlon*, C. Palmer*, Y. Pan*, B. Keeshan*, and G. Spatafora. 2006. The SloR/Dlg metalloregulator modulates Streptococcus mutans virulence gene expression. J. Bacteriol. 188:5033-5044.