Esther Bullitt, Ph.D.
Associate Professor of Physiology & Biophysics
- Title Associate Professor of Physiology & Biophysics
- Office W341A
- Email firstname.lastname@example.org
- Phone (617) 358-8464
- Education A.B. Grinnell College
Ph.D. Brandeis University
Working Together to Promote an Inclusive Community
AS PRESIDENT OF THE MICROSCOPY SOCIETY OF AMERICA, I SUPPORT EQUITY AND INCLUSION, AND THE BLACK LIVES MATTER MOVEMENT, AS STATED IN THE LETTERS BELOW.
Please note: The views expressed in the document below are my own, and those who have signed their names.
During a time when we are unable to gather in person, we are uplifted by seeing our young leaders working together to promote an inclusive community.
MSA Council created a Student Council in 2017, with the primary motivation of giving voice to the next generation of microscopists. The leaders of the MSA Student Council have used that voice to collaboratively write the letter below, stating their unwavering support to those facing racial injustices, specifically to those belonging to Black communities and other communities of color both in the United States and abroad. Their leadership and vocal stance against racism gives us hope for the future of not only our society, but of the global community.
As a community, MSA values each of our members, and we realize it is imperative to foster a welcoming and inclusive environment. Now more than ever, doing so requires us to move beyond self-reflection and take action. To that end, we have established an equity task force. This task force will evaluate our practices, language and decisions, and provide detailed recommendations on how we as a society can improve our culture of inclusivity. This is not work that can be done overnight, but it is work that requires urgent and ongoing action today, tomorrow and all the days that follow. While it is the responsibility of the leadership to take these first steps, we ask you to join us in our efforts to produce large and lasting change in this movement towards equity.
We look forward to seeing you in August at our virtual Microscopy & Microanalysis meeting.
Esther Bullitt, MSA President
Peter Crozier, MSA President-Elect, and Student Council Liaison
From the Microscopy Society of America Student Council:
To our Microscopy Community,
We add our voices in solidarity with the Black community and communities of color, who are so terribly affected by the racism and inequality that still exists.
In Science, progress requires all levels of diversity – diversity of thought, of viewpoint, of background, of experience, of talent. Success requires interdisciplinary teams, with each member listening to the others and working in a closely coordinated way. We therefore celebrate diversity, and work to increase the voices and safety of those who have been marginalized.
How can we help combat racism and injustice? Education, compassion, empathy, opening our eyes to the reality of our world, and working for change.
The MSA Student Council helps define the future of our society. This is a responsibility that requires we do not take the issues of racism and injustice lightly. We see our society as a place for individuals, no matter their race, to discuss important scientific questions. We aim to be as active in cultivating a welcoming community as we are in pursuing scientific knowledge. In fact, we know that without a diverse community we will not be able to answer the most critical questions. This is not a feeling, this is a fact that has been proven many times over.
While we are proud of what we have achieved in the few years of our existence, we must do better and reflect on our own practices and culture to ensure that we are actively promoting equality and rejecting hate. This is not a goal that can be achieved passively, nor can this be achieved by just a few members. This ideal must be continually and actively pursued by our community.
We hope that all MSA members will join us in making a commitment to working towards not only a scientific community, but a world that is more just, equitable, and safe for everyone. Without the commitment of the whole, we leave our colleagues vulnerable to the heavy and dangerous burden of discrimination. Silence is not the answer to acts of social injustice, we can only change through great acts of love and standing in support of those who are working towards a better future.
Change is a multi-lane road, and we implore you to commit to a path that suits you―stand up against injustice, amplify the voices of change makers, educate yourself, or donate to civil rights organizations.
MSA Student Council
Bullitt Lab Research
Protein Structure Facilitates Function
Using Electron Microscopy and Quantitative Image Analysis to see how Macromolecular Assemblies Work
Structural studies of biological macromolecular assemblies are providing a deeper understanding of cellular function. In our laboratory, we utilize electron microscopy and image reconstruction to investigate questions about:
- how adhesion pili aid pathogenic bacterial survival
- how viruses impact cellular processes
- how the type III secretion system is assembled, leading to secretion of toxins
BACTERIAL ADHESION PILI
YouTube: the role of basic research in developing a vaccine against Traveler’s Diarrhea: Vaccine from basic research
Fibers on the surfaces of many pathogenic bacteria can overextend like a toy Slinky, whereas homologous proteins on bacteria that cause pneumonia, ear infections, and meningitis assemble into a 3-stranded rope-like fibers (blue). In collaboration with Dr. Magnus Andersson’s lab at Umeå University in Umeå Sweden we have shown that the forces required for unwinding pili (also called ‘fimbriae’) are specific for the pilus-type, and thus vary with the microenvironment expected to be encountered. For example, CFA/I pili on diarrhea-causing intestinal bacteria unwind at less than one-third the force required to unwind P-pili expressed on urinary tract infection bacteria.
Our structural studies now show the structure of CFA/I pili at 4.2 A resolution:
As more bacteria become resistant to antibiotics, it is essential to develop novel approaches for prevention and treatment of infection. Structural studies are vital for discovering clues to how bacteria bind, and how they remain attached while the host is trying to remove them. We are examining the architecture of bacterial adhesion pili and investigating small molecules that disrupt their assembly and/or function.
Bullitt, E., L. Makowski (1995). Structural polymorphism of bacterial adhesion pili. Nature 373:164-167. PMID: 7816100
Mu, X.Q. and E. Bullitt (2006). Structure and assembly of P-pili: a protruding hinge region used for assembly of a bacterial adhesion filament. Proc. Natl. Acad. Sci. USA 103:9861-9866. PMCID: PMC1502544
Mu, X.Q., S.J. Savarino, E. Bullitt (2008). The three-dimensional structure of CFA/I adhesion pili: Traveler’s Diarrhea Bacteria Hang on by a Spring. J. Mol. Biol. 376:614-620. PMCID: PMC2265596
Li, Y-F, S. Poole, K. Nishio, K. Jang, F. Rasulova, A. McVeigh, S.J. Savarino, D. Xia, E. Bullitt (2009) Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli. Proc. Natl. Acad. Sci. USA 106: 10793-10798. PMCID: PMC2705562
Andersson M, O. Björnham, M. Svantesson, A. Badahdah, B.E. Uhlin, E. Bullitt (2012). A Structural Basis for Sustained Bacterial Adhesion: Biomechanical Properties of CFA/I Pili. J. Mo.l Biol. 415: 918-928. PMCID: PMC3267891
TYPE III SECRETION
Only 10 bacteria (or fewer!) are needed for Shigella flexneri to cause dysentery (bloody diarrhea). This disease is initiated via the type III secretion system, which is used to secrete both toxins and bacterial effectors that alter normal host cell functions to promote bacterial growth and spread.
To understand (and disrupt) the process of infection, we are examining assembly intermediates of the T3SS syringe-like needle and its tip structure. Through our collaborations with the Picking lab at Oklahoma State University Stillwater and the Geisbrecht lab at the University of Missouri Kansas City we have shown that IpaD, the first protein that localizes to the needle tip, is present as a pentamer, and undergoes a dramatic conformational change as compared to the structure that has been solved by x-ray crystallography.
The structures of three-dimensional reconstructions of immature and nascent needle tips show clearly IpaD as an elongated pentameric structure.
This new result demonstrates that the distal domain of IpaD flips up, as compared to the structure solved by X-ray crystallography (pdb 2j0o).
Diagram to the right shows the conformational change of the distal domain that is needed to fit the crystal structure of IpaD into our density map of 3-dimensional reconstructions from electron microscopy data.
Epler, C.R., N.E. Dickenson, E. Bullitt*, W.L. Picking* (2012). Ultrastructural analysis of IpaD at the tip of the nascent MxiH type III secretion apparatus of Shigella flexneri. J. Mol. Biol. 420:29-39. PMID: 22480614 *corresponding authors
The poliovirus polymerase, 3Dpol, is an RNA-dependent RNA polymerase. Its structure is similar to other polymerases, and can be described as a right hand. We are investigating the role of two-dimensional 3Dpol lattices in replication, using electron microscopy and image processing of tubes and sheets formed in vitro. The crystal structure shown was solved in Steve Schultz’s lab, pdb 1rdr.
In collaboration with Dr. Karla Kirkegaard’s lab at Stanford University we have shown that
1) 3Dpol forms two-dimensional lattices that we expect facilitate replication by concentrating substrate and enzyme onto a two-dimensional surface, the vesicular membrane,
2) “Zombie” 3Dpol protein (dead active site) can support assembly of oligomers and restore replication when the wild type protein concentration is too low to do so.
Lyle, J.M.*, E. Bullitt*, K. Bienz, K. Kirkegaard (2002). Visualization and functional analysis of RNA-dependent RNA polymerase lattices. Science 296:2218-2222. *these authors contributed equally
Spagnolo, J.F., E. Rossignol, E. Bullitt, K. Kirkegaard (2010). Enzymatic and non-enzymatic functions of viral RNA-dependent RNA polymerases within oligomeric arrays. RNA 16:382-393. PMCID: PMC2811667
Tellez, A.B*., J. Wang*, E.J. Tanner, J.F. Spagnolo, K. Kirkegaard+ and E. Bullitt+ (2011). Interstitial Contacts in an RNA-Dependent RNA Polymerase Lattice. J Mol Biol 412(4): 737-50. PMID: 21839092. http://www.ncbi.nlm.nih.gov/pubmed/21839092.
*these authors contributed equally, +corresponding authors
Andersson M, Björnham O, Svantesson M, Badahdah A, Uhlin BE, Bullitt E. (2012). A Structural Basis for Sustained Bacterial Adhesion: Biomechanical Properties of CFA/I Pili., J Mol Biol. 2012 Feb 3;415(5):918-28.
Tellez AB, Wang J, Tanner EJ, Spagnolo JF, Kirkegaard K, Bullitt E. (2011). Interstitial contacts in an RNA-dependent RNA polymerase lattice. J Mol Biol. 2011 Sep 30;412(4):737-50.
Li, Y-F, S. Poole, K. Nishio, K. Jang, F. Rasulova, A. McVeigh, S.J. Savarino, D. Xia, E. Bullitt (2009). Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli. Proc. Natl. Acad. Sci. 106:10793-10798.
Mu X.Q., S.J. Savarino, E. Bullitt (2008). The three-dimensional structurel of CFA/I adhesion pili: Traveler’s diarrhea bacteria hang on by a spring. J. Mol. Biol. 376:614-620.
Verger, D., E. Bullitt, S.J. Hultgren, G. Waksman (2007). Crystal structure of the P pilus rod subunit PapA. PLoS Pathogens 3:e73(674-682).
Mu XQ and E. Bullitt (2006). Structure and assembly of P-pili: a protruding hinge region used for assembly of a bacterial adhesion filament. Proc. Natl. Acad. Sci.103:9861-9866.
Mu X.Q., E.H. Egelman, E. Bullitt (2002). Structure and Function of Hib Pili from Haemophilus influenzae Type b. J Bacteriol. 184:4868-74.
Lyle J.M., E. Bullitt, K. Bienz, K. Kirkegaard (2002). Visualization and functional analysis of RNA-dependent RNA polymerase lattices. Science. Jun 21;296(5576):2218-22.
Bullitt E., M.P. Rout, J.V. Kilmartin, C.W. Akey(1997). The yeast spindle pole body is assembled around a central crystal of Spc42p. Cell Jun 27;89(7):1077-86.
Bullitt E, L. Makowski (1995). Structural polymorphism of bacterial adhesion pili. Nature Jan 12;373(6510):164-7.
Department of Physiology & Biophysics
Boston University School of Medicine
700 Albany Street
Boston MA 02118-2526
Phone: (617) 358-8464