Pamela A. Silver, Ph.D.
|Title||Elliott T. and Onie H. Adams Professor of Biochemistry and Systems Biology|
|Institution||Harvard Medical School|
|Address||Harvard Medical School|
Systems Biology Alpert 536
200 Longwood Ave
Boston MA 02115
Available: 09/10/12, Expires: 12/20/13
There is a growing need for rapid response vaccines because of the increase in unconventional pathogens, emerging viruses and potential pandemics. Problems with current standard vaccines include the fact that single-subunit vaccines do not offer complete protection and attenuated live vaccines can revert or evolve, are dangerous to immunosuppressed individuals and need cold storage.
Our plan is to construct a defined polyvalent vaccine nanoparticle that will look like an infectious agent to the immune system. It will contain multiple copies of multiple antigens, can be taken up by antigen presenting cells, will stimulate the immune system to give the desired response and will be biologically inert. The rapid response anti-viral agents will consist of oligonucleotides and designer protein assemblies. The project will consist of a combination of protein and nucleotide design, expression and purification of proteins and assembly of the novel structures.
Available: 10/01/12, Expires: 12/31/13
In general, our laboratory is interested in the predictable engineering of cells and organisms to solve real world problems. In brief, these include engineering of human cells to carry out programs in response to disease and environment, the engineering of biological sensors to record disease states, the green production of food, fuel and drugs, and the engineering of therapeutic proteins. Some details on some current projects are provided below but it is recommended that interested students contact Professor Silver directly to discuss possible projects.
One project focuses on building a biological counter. One possible method for controlling the expression of a genetic circuit in mammalian cells is by temporally separating the expression of the circuits during each mammalian cell cycle. This can be accomplished by fusing modular, cell-cycle specific protein degradation tags (degrons). To test the modularity of these degrons and generate a library of usable parts, we have generated both N- and C- terminal fusions of each of these domains with several different fluorescent proteins. When these fluorescently tagged degrons are fused with components of a synthetic genetic circuit, such as a ZnF activator or repressor, the circuit can be temporally controlled and monitored in real-time via fluorescent readout.
A second project has as its goal to create gene-based memory devices that can record the environmental experiences of bacteria. These devices would be used to protect bacterial strains that have been metabolically engineered to produce commodity chemicals and drugs, and also to control the dissemination of pathogenic bacteria that may be under study. The proposed work grows out of synthetic-biological construction of microbial memory systems that has demonstrated, at a qualitative level, that such devices can be made.
A third project involves the novel use of nucleic acid scaffolds both in tissue engineering and in intracellular programming.
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