Research Projects
Viruses & other Protein Cage Architectures as Templates for Materials Synthesis
Viruses, and other protein cage architectures, have emerged as platforms for synthetic manipulation with a range of applications from materials to medicine. The use of protein cages as synthetic templates utilizes their inherent properties. An appreciation of these properties has resulted in a paradigm shift from the study of viruses as disease causing agents to highly useful molecular assemblies, which can be chemically and genetically modified. Synthetic manipulation can impart new function to protein cages, combining the best of evolution and truly intelligent design.
Viruses, and protein architectures like ferritin, Dps, and small heat shock proteins can be viewed as molecular containers with three distinct interfaces that impart function (and can be synthetically manipulated). These are: the exterior surface, the interior surface, and the interface between the subunits that make up the overall architecture. These protein cage architectures have been used as constrained reaction environments for the synthesis and sequestration of nanomaterials, the encapsulation of therapeutic drugs, and diagnostic imaging agents. While the interior surfaces can be manipulated to direct encapsulation of a cargo, the outer surfaces have been used to incorporate targeting moieties to direct and target specific surfaces including cells and solid supports. The interface between subunits can influenced to promote disassembly, and reassembly into a wide range of alternate architectural assemblies or which can incorporate metal binding sites.
Recent work in the lab has also focused on the development and use of protein cages, isolated from hyperthermophilic microorganisms, some of which are stable to temperatures up to 120ºC.
Selected Reviews:
1. T. Douglas, M. Young “Viruses: Making Friends With Old Foes” Science (2006) 312, 873-875. [Cover]
2. M. Uchida, M.T. Klem, M Flenniken, M. Allen, Z. Varpness, E. Gillitzer, P. Suci, M. Young and T. Douglas “Biological Containers: Protein Cages as Multifunctional Nanoplatforms” Advanced Materials (2007) 19, 1025-1042.
3. M.T. Klem, M. Young, T. Douglas “Biomimetic Approaches to the Synthesis of Magnetic Nanoparticles” Materials Today (2005) 8, 28-37.
4. M. Young, D. Willits, M. Uchida, T. Douglas “Plant Viruses as Biotemplates for Materials and Their Use in Nanotechnology” Annual Reviews in Phytopathology (2008) 46, 361-368.
5. B. Wiedenheft, M. Flenniken, M.A.Allen, M. Young, T. Douglas “Bioprospecting in high temperature environments; application of thermostable protein cages“ Soft Matter (2007) 3, 1019-1098.
Personnel:
Trevor Douglas
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