Sarah Bondos, PhD
Education and Post-Graduate Trainingp>Dr. Sarah Bondos received her BS in chemistry with honors and distinction from the University of North Carolina in 1993, and her PhD in biochemistry from the University of Illinois in 1998 working with Dr. Stephen Sligar and Dr. Jiri Jonas. Her postdoctoral work was at Rice University, working with Dr. Kathleen Matthews.
Tissue-specific regulation of protein function
During animal development, the Hox transcription factor family determines the identity and guides the formation of many different types of tissues. Because individual members of the Hox protein family define drive the development of multiple types of tissues and organs, each Hox protein must be able to infer their location within the animal and specifically and reliably respond by regulating the appropriate subset of target genes. Misregulation of this process can lead to abnormalities or death in developing animals, or promote carcinogenesis and impede wound repair in adults. Our lab is determining how regions outside the DNA-binding homeodomain of the Drosophila Hox protein Ultrabithroax (Ubx) enhance DNA binding specificity and respond to conformational changes, tissue-specific alternative splicing, protein interactions, and cell signaling cascades. Many of these regulatory mechanisms involve intramolecular interactions between the structured homeodomain and intrinsically disordered (unstructured) regions of the Ubx. We are exploring these mechanisms in vitro and in vivo using a combination of biophysical, cell biological, and genetic approaches.
Functionalizable protein-based materials
We have also developed methods self-assemble Ubx protein into novel biomaterials. These materials hierarchically self-associate into structures ranging from nanoscale fibrils to macroscale fibers, films, and meshes. Because Ubx self-assembles in mild aqueous buffers, we can use standard molecular biology techniques to create fusion proteins, in which a single polypetide encompasses the sequence of Ubx and a functional protein. These fusion proteins are capable of both self-assembly and the function of interest, and thus represent a facile method to functionalize and pattern materials. Ubx materials also bind DNA and nanoparticles, further expanding the range of functionalities that can be incorporated into these materials. We are currently developing Ubx materials as tissue engineering scaffolds and biosensors.
Graduate training is available through the Medical Science PhD program(College of Medicine), through the MD/PhD program (College of Medicine) and other programs that our faculty are affiliated with joint research.
- Howell DW, Tsai SP, Churion K, Patterson J, Abbey C, Atkinson JT, Porterpan D, You YH, Meissner KE, Bayless KJ, Bondos SE (2015) Adv. Funct. Mater. 25, 5988-5998.
- Bondos SE, Swint-Kruse L, Matthews KS (2015) Flexibility and disorder in gene regulation: LacI/GalR and Hox proteins. J. Biol. Chem. 290, 24669-24677. http://www.ncbi.nlm.nih.gov/pubmed/26342073
- Xie XJ, Hsu FN, Gao X, Xu W, Ni JQ, Xing Y, Huang L, Hsiao HC, Zheng H, Wang C, Zheng Y, Xiaoli AM, Yang F, Bondos SE, Ji JY (2015) CDK8-Cyclin C mediates nutritional regulation of developmental transitions through the ecdysone receptor. PLoS Biol. 13, e1002207. http://www.ncbi.nlm.nih.gov/pubmed/26222308
- Niklas KJ, Bondos SE, Dunker AK, Newman SA (2015) Rethinking gene regulatory networks in light of alternative splicing, post-translational modifications, and intrinsically disordered protein domains. Front. Cell Dev. Biol. 3, 8. http://www.ncbi.nlm.nih.gov/pubmed/25767796
- Tsai SP, Howell DW, Huang Z, Hsiao HC, Lu Y, Matthews KS, Lou J, and Bondos SE (2015) The effect of protein fusions on the production and mechanical properties of protein-based materials. Adv. Funct. Mater. 25, 1442-1450.
- Dunker AK, Bondos SE, Huang F, Oldfield CJ (2015) Intrinsically disordered proteins and multicellular organisms. Semin. Cell Dev. Biol. 37, 44-55. http://www.ncbi.nlm.nih.gov/pubmed/25307499
- Patterson J, Arenas A, Wang TY, Hsiao HC, Pellois JP, Rice-Ficht A, and Bondos SE (2015) Materials composed of the Drosophila Hox protein Ultrabithorax are biocompatible and non-immunogenic. J. Biomed. Mater. Res. Part A 103, 1546-1553. http://www.ncbi.nlm.nih.gov/pubmed/25087647
- Churion K, Hsiao HC, Matthews KS, Bondos SE (2014)Measuring Hox-DNA binding by electrophoretic mobility shift analysis. Methods Mol. Biol. 1196, 211-230. http://www.ncbi.nlm.nih.gov/pubmed/25151166
- Patterson JL, Abbey CA, Bayless KJ, Bondos SE (2014) Materials composed of the Drosophila melanogaster protein Ultrabithorax are cytocompatible. J. Biomed. Mater. Res. Part A 102, 979-104. http://www.ncbi.nlm.nih.gov/pubmed/23596050
- Hsiao HC, Catanese DJ, Jordy KJ, Gonzalez KL, Matthews KS, and Bondos SE (2014) Intrinsically disordered regions select protein interactions by topology PLoS ONE 9, e108217. http://www.ncbi.nlm.nih.gov/pubmed/25286318
- Churion K and Bondos SE (2014) Identifying solubility-promoting buffers for intrinsically disordered proteins prior to purification. Methods Mol. Biol. 896, 415-427. http://www.ncbi.nlm.nih.gov/pubmed/22821541
- Dunker AK, Babu MM, Barbar E, Blackledge M, Bondos SE, Dosztányi Z, Dyson HJ, Forman-Kay J, Fuxreiter M, Gsponer J, Han KH, Jones DT, Longhi S, Matello SJ, Nishikawa K, Nussinov R, Obradovic Z, Pappu RV, Burkhard R, Selenko P, Subramaniam V, Sussman JL, Tompa P, and Uversky VN (2013) What’s in a name? Why these proteins are intrinsically disordered. Intrinsically Disordered Proteins 1, e24157.
- Majithia R, Patterson J, Bondos SE, and Meissner KE (2011)On the design of composite protein-quantum dot composite biomaterials via self-assembly. Biomacromolecules 12, 3627-3637. http://www.ncbi.nlm.nih.gov/pubmed/21892824
- Liu Y, Merchant Z, Hsiao HC, Gonzalez KL, Matthews KS, and Bondos SE (2011) Media source profoundly influences the outcome of yeast one- and two-hybrid experiments. Biol. Proced. Online 13, 6. http://www.ncbi.nlm.nih.gov/pubmed/21843345
- Fuxreiter M, Istvan S, Bondos SE (2011) Dynamic protein-DNA recognition: beyond what can be seen. Trends Biochem. Sci. 36, 415-423. http://www.ncbi.nlm.nih.gov/pubmed/21620710
- Huang Z, Salim T, Brawley A, Patterson J, Matthews KS, Bondos SE (2011) Functionalization and patterning of protein-based materials using active Ultrabithorax. Adv. Funct. Mater. 21, 2633-2640.
- Huang Z, Lu Y, Majitha R, Shah J, Meissner K, Matthews KS, Bondos SE, and Lou J (2010) Size dictates mechanical properties for fibers self-assembled by the Drosophila Hox transcription factor Ultrabithorax. Biomacromolecules 11, 3644-3651. http://www.ncbi.nlm.nih.gov/pubmed/21047055
- Liu Y, Matthews KS, Bondos SE (2009) Internal regulatory interactions determine DNA binding specificity by a Hox transcription factor. J. Mol. Biol. 390, 760-774. http://www.ncbi.nlm.nih.gov/pubmed/19481089
- Greer AM, Huang A, Oriakhi A, Lu Y, Lou J, Matthews KS, and Bondos SE (2009) The Drosophila transcription factor Ultrabithorax self-assembles into protein-based biomaterials with multiple morphologies. Biomacromolecules 10, 829-837. http://www.ncbi.nlm.nih.gov/pubmed/19296655
- Liu Y, Matthews KS, and Bondos SE (2008)Multiple intriniscally disordered sequences alter DNA binding by the homeodomain of the Drosophila Hox protein Ultrabithorax J. Biol. Chem. 283, 20874-20887. http://www.ncbi.nlm.nih.gov/pubmed/18508761
- Bondos SE, Tan XX, and Matthews KS (2006) Physical and genetic Interactions link Hox function with diverse transcription factors. Mol. Cell. Proteomics. 5, 824-834. http://www.ncbi.nlm.nih.gov/pubmed/16455680
Graduate Research Assistants
- Kelly Churion
- Hao-Ching Hsiao
- Shang-Pu Tsai
Associate Research Specialist
- Jan Patterson