Grace Spatafora
Office
McCardell Bicen Hall 354
Tel
(802) 443-5431
Email
spatafor@middlebury.edu
Office Hours
Fall 2022: Monday 10:00am - 12:00pm or by appointment
Additional Programs
Academic Affairs Biology Molecular Biology and Biochemistry

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 2018, Fall 2022

Requirements

DED, SCI

View in Course Catalog

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

Winter 2020, Spring 2022

Requirements

SCI

View in Course Catalog

Course Description

Microbiology
The microbiological principles emphasized in this class will provide students with a foundation for advanced study in many areas of contemporary biology. The course will integrate basic and applied aspects of microbiology into a study of the prokaryotic microorganisms. General principles of bacterial cell structure, function, and the role of microorganisms in industry, agriculture, biotechnology, and disease will be discussed. An independent laboratory project will stress basic microbiological techniques as applied to the isolation, characterization, and identification of microorganisms from the natural environment. (BIOL 0140 and BIOL 0145) 3 hrs. lect./4 hrs. lab./1 hr. prelab.

Terms Taught

Fall 2019

Requirements

CW, SCI

View in Course Catalog

Course Description

Molecular Genetics
This course will focus on the structure and function of nucleic acids in both prokaryotes and eukaryotes. Lectures will center on molecular mechanisms of mutation, transposition, and recombination, the regulation of gene expression, and gene control in development, immune diversity and carcinogenesis. Readings from the primary literature will complement the textbook and classroom discussions. The laboratory will provide training in both classic and contemporary molecular-genetic techniques including nucleic acid isolation and purification, cloning, electroporation, nick-translation, Southern/Northern blotting, DNA sequencing, PCR and RT-PCR. (BIOL or MBBC majors, or by waiver. BIOL 0140 and BIOL 0145 or waiver) 3 hrs. lect./4 hrs. lab./1 hr. prelab.

Terms Taught

Spring 2019, Spring 2020

Requirements

SCI

View in Course Catalog

Course Description

Mechanisms of Microbial Pathogenesis
Many microorganisms have the potential to cause disease. An understanding of the mechanisms that promote bacterial pathogenesis is therefore essential for the development of effective disease prevention and/or treatment strategies. This course will explore the mechanisms by which microbial pathogens adhere to, invade, and persist in the human host. While an emphasis will be placed on microbial mechanisms of disease, the host response to the infectious process will also be discussed. (BIOL 0140 and BIOL 0145) 3 hrs lect/disc.

Terms Taught

Winter 2019

Requirements

SCI

View in Course Catalog

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 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023

View in Course Catalog

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 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023

View in Course Catalog

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 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023

View in Course Catalog

Course Description

Shaping the Future
The release of genetically engineered organisms into the environment has great potential for agriculture and industry; however, the consequences posed by the transfer of genetic material from one organism to another on the inter-relationships within an ecosystem remain largely uncertain.  Gene therapy represents a major molecular-genetic advancement for medical science, yet there is much controversy regarding its safety and whether its use for the purpose of “enhancement” constitutes an ethical application for this technology.  New reproductive technologies use genetic engineering to conceive life in a petri dish and select against embryos with inherited disease, which has had considerable social, political, and ethical impacts.  This course will use writing, in-class discussion, and hands-on experiences in the laboratory as tools to explore these and other biotechnological advances and their social implications.  Writing exercises will emphasize the ethical considerations brought about by the Human Genome Project, DNA fingerprinting, and the introduction of edible vaccines to grocery store shelves to name a few. 3 hrs. sem.

Terms Taught

Fall 2019

Requirements

CW, SCI

View in Course Catalog

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

View in Course Catalog

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 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023

View in Course Catalog

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 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Winter 2021, Spring 2021, Fall 2021, Winter 2022, Spring 2022, Fall 2022, Winter 2023, Spring 2023

View in Course Catalog

Publications

Select Publications:

*Indicates a Middlebury College student

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.