User:Jessie Wang: Module 3

Module 3 Primary Research Project

Becky Kusko and Jessie Wang

Research Project Proposals

Idea 1: Cancerphilic Bacteria

• It has long been known that bacteria use external signals to decide when to invade cells, and that bacteria can release proteins into the cells they invade. Using genetic engineering and synthetic biology, these two functions of bacteria could be used as a therapy for cancer. Many cancers are known to have heavily overexpressed or mutant surface proteins. Bacteria could be engineered to only recognize cells with surface proteins indicative of cancer. Moreover, the bacteria could be further mutated to release a cytotoxic agent upon entering the cell, or cause lysis/apoptosis.
• Reference: Anderson, J. C., Clarke, E. J., Arkin, A. P., Voigt, C. A. “Environmentally controlled invasion of cancer cells by engineered bacteria” J. Mol Biol., 355(4), 619-27, 2005. PMID: 16330045

Idea 2: siRNA-mediated Antiviral Therapy

• Recently, scientists have turned to siRNA-mediated RNAi as a possible treatment against viral diseases. A group from China developed siRNAs that targeted the ORF7 gene (a gene having to do with viral replication) of the porcine reproductive and respiratory syndrome virus. Using western blot, immunofluorescence and FQ-PCR, they confirmed that expression of the gene was reduced.
• This same idea should be able to be applied to the Epstein-Barr virus, a virus that is involved with mononucleosis and some cancers. The siRNA may be used to target the virus's lytic/lysogenic cycles.
• Possible gene targets include: BZLF1 (the main activator of the lytic cycle); BGLF4 (involved in lytic cycle); LMP1, Akt, NFkappaB, and Stat3 (latent cycle);

References:

• He YX, Hua RH, Zhou YK, Qiu HJ, Tong GZ. “Interference of porcine reproductive and respiratory syndrome virus replication on MARC-145 cells using DNA-based short interfering RNAs.” Antiviral Res. 2007 May;74(2):83-91. Epub 2006 May 11. PMID: 16730075
• Terrin L, Dolcetti R, Corradini I, Indraccolo S, Col JD, Bertorelle R, Bonaldi L, Esposito G, De Rossi A. "hTERT inhibits the Epstein-Barr virus lytic cycle and promotes the proliferation of primary B lymphocytes: implications for EBV-driven lymphomagenesis." Int J Cancer. 2007 Aug 1;121(3):576-87. PMID: 17417773
• Gershburg E, Raffa S, Torrisi MR, Pagano JS. "Epstein-Barr virus-encoded protein kinase (BGLF4) is involved in production of infectious virus." J Virol. 2007 May;81(10):5407-12. Epub 2007 Mar 14. PMID: 17360761
• Shair KH, Bendt KM, Edwards RH, Bedford EC, Nielsen JN, Raab-Traub N. "EBV Latent Membrane Protein 1 Activates Akt, NFkappaB, and Stat3 in B Cell Lymphomas." PLoS Pathog. 2007 Nov 9;3(11):e166. PMID: 17997602