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Living Bioreactor for Stoichiometric Protein Production

Living bioreactors are powerful systems for producing a variety of valuable compounds. The versatility of such bioreactors is one of the more useful aspects of the system. Large quantities of compounds or cellular components can be produced efficiently, with minimal cost. Alternately, these systems can be used to produce pathway components that are necessary in the production of secondary products. A common problem with such systems is that they are limited by non-uniform production of pathway components, or require an isolation process to ensure the components are in the appropriate quantity and sequence in the process. Inventors at Texas A&M and UC San Francisco have developed a novel technique to address these issues. The technology effectively results in a stoichiometric production of protein components that are produced in an array, ready for secondary production.

Collaboration Opportunity: Novel Mouse Models of Human Hepatitis B Virus Infection for Drug Discovery and Vaccine Research

HBV infection can lead to chronic infections that result in 0.6 million deaths per year worldwide by causing liver failure and cancer. Clearance of HBV infection is age dependent, with the majority of adult-acquired infections leading to spontaneous clearance, whereas infection in young children often leads to chronic infections. To study these early events of infection and immune activation that lead to HBV clearance or persistence, in vivo models are needed to screen and validate lead drug candidates. HBV cannot infect mice, however, researchers at UCSF have generated transgenic mouse models that mimic critical features of primary HBV infection observed in humans.

Novel, Immunogenic Epitopes for use in an HIV Vaccine

The Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate maker that could be used to target any HIV-infected cell regardless of its mutational status. In this regard, scientists have recently focused their attention on so-called cryptic peptides of HIV.  Cryptic peptides are non-functional HIV proteins that are produced due to translational errors that occur in HIV-infected cells.  Because these cryptic peptides are commonly produced and then presented on the surface of the HIV-infected cells, it is thought they may be good surrogate markers and targets for any HIV-infected cell.

Novel Peptides for Development of HIV Vaccine and Therapy

Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate marker that could be used to target any HIV-infected cell regardless of its mutational status. In this regard, scientists have recently turned their attention to the APOBEC machinery in HIV cells.  APOBEC proteins are human proteins that modify genetic material of viruses so that they are unable to produce proteins essential for viral survival.  Remarkably, HIV evades the APOBEC defense by making a protein called Vif that re-routes APOBEC proteins to proteosomes for destruction thereby reducing APOBEC's protective functions.  However, this activity also increases the presentation of APOBEC antigens or peptides on the cell's surface. APOBEC peptides may be good candidates for surrogate HIV markers simply because they are present on the surface of all HIV-infected cells.  In addition, in order for HIV-infected cells to stop displaying APOBEC peptides on their surface, the virus would need to evolve mutations in the region coding for the Vif protein that re-routes the APOBEC proteins.  This would make the virus vulnerable to the defenses mediated by the functional APOBEC proteins.  This phenomenon should result in dual pressure on the virus that should slow or prevent the evolution of viral resistance to these T-cell responses.

Apicoplast-Deficient, Attenuated Strains of Plasmodium for Use as Malaria Vaccines

Currently, no malaria vaccines are available for clinical use. The need for a vaccine is also compounded by the emergence of multiple drug-resistant Plasmodium strains. In 2008, there were nearly 250 million cases of malaria and one million deaths worldwide according to the World Health Organization. Moreover, in addition to chloroquine resistance, resistance to newer anti-malarials is growing. Thus, innovative vaccines and anti-malarials are needed to reduce the morbidity and mortality caused by malaria infections in humans.

PSEUDOMONAS AERUGINOSA VACCINE

Pseudomonas aeruginosais an opportunistic bacterial pathogen responsible for 10% of all nosocomial (hospital-acquired) infections, a leading cause of nosocomial pneumonia in general patient populations, and the leading cause in intensive care patient populations. Since Pseudomonas is often resistant to antibiotics, an infection is life-threatening for compromised individuals such as burn victims, AIDS patients, and patients with cystic fibrosis. Respiratory failure, the leading cause of cystic fibrosis-associated death, results from chronic Pseudomonas infections that lead to lung damage as bacterial toxins attack lung epithelia. This damage then allows the infection to spread beyond the lungs. A secretion/intoxication system present on the bacterial surface transports toxins directly into epithelial cells, and a well-documented inhibition of this system through blockade of the bacterial toxin transport component PcrV provides demonstrable protection against lung injury and increased survival in animal models. Researchers at the University of California, San Francisco have shown that the PcrV protein is a highly effective vaccination agent against Pseudomonas, whether administered before or after infection.

HUMAN IMMUNOSTIMULATORY T CELLS

Research into modulating immune function through immunostimulatory T cells has been hampered by the lack of identification of the molecular markers on such cells. UCSF investigators have identified a novel endogenous human T cell population that can significantly enhance the proliferative capacity of a T cell response. In contrast to T cells that can be induced to suppress a proliferative response, these are a naturally occurring, functionally mature T-cell subpopulation that induce the proliferation of a T cell.

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