Utilize synthetic biology principles for addressing fundamental medical needs; engineered photosynthetic bacteria to harness solar energy to drive synthesis of hydrogen, biofuels and chemicals. 

Dr. Silver’s current studies have enormous practical as well as therapeutic applications. The lab has become expert in utilizing synthetic biology principles for addressing fundamental medical needs. The lab is pioneering the development of artificial protein ligands of cell surface receptors that promote binding with increased cell-type specificity. This strategy is aimed at minimizing undesirable clinical manifestations; consequently, the therapeutic implications are immense. 

The global depletion of fossil fuels has ignited the exploration for alternative, environmentally-friendly, energy sources that can be harnessed at a fraction of the cost of oil. The solar biogenerator bacterial cell developed in the Silver lab enables low cost and large scale production of biofuels, hydrogen and other chemcials. These products can be employed as sources of energy, active ingredients in the food, cosmetics, chemical and pharmaceutical industries. The Silver solar biocell does not require any biomass: its feedstock is merely water and atmospheric CO₂. 
 

 

The lab’s studies on signal transduction and alternative splicing complement its interest in modeling signaling pathways in pathological states, such as cancer, and are illuminating molecular mechanisms of disease. Moreover, its innovative strategy to exploit biological organisms as “bioreactors” and photosynthesis as an energy and carbon source may have significant practical applications.

• Intermixing principles of quantitative systems biology and synthetic biology to achieve cell targeting specificity and improved therapeutic potential, by constructing artificial chimeric receptor ligands having modified binding activity (generated through specific genetic alterations).
   
• Applying synthetic biology to building comoputational devices (e.g., a biologic sensor that operates through a transcriptional-controlled circuit and is maintained in successive generations).
   
• Investigating the regulation of alternative mRNA splicing in a systems-wide approach, to gain insights into the genetic mechanisms underlying the etiology of disease.
   
• Studying epigenetic mechanisms that control gene expression, in normal and pathological states.
   
• Exploring genetically-engineered photosynthetic bacteria as a metabolic generator of hydrogen, biofuels, and high value chemicals

Dr. Silver’s laboratory has had a prolific publication record, reflecting significant success in experimentally addressing diverse and complex biological questions posed by  molecular, cellular, and systems biology. The lab has made important contributions to the understanding of gene expression, cellular regulatory mechanisms, and synthetic biology. The lab focuses on the relationship of transcriptional activity to nuclear organization. In one recent study, the lab has demonstrated that histone deacetylases have the ability to modulate the spatial relationship between specific genomic regions and nuclear pore complexes, revealing regulatory pathways that integrate nuclear pore architecture and gene regulation. These findings extend the lab’s earlier work that linked global transcriptional activity and nuclear organization.

The lab has also had a longstanding interest in mechanisms of gene expression. The lab has uncovered novel proteins involved in the export of processed mRNA from the nucleus, while illuminating a coordination of mRNA export, cell cycle dynamics, and protein translation. Other investigations into gene expression have shown that the transcriptional apparatus can “sense” fluctuating metabolic conditions via compensatory exon expression/usage, thus revealing  mechanisms of molecular acclimation. Another core scientific undertaking in the lab has been in the field of synthetic biology, where they have taken creative approaches for modulating cellular outputs, capitalizing on well-studied molecular pathways.
 

Biological Mechanisms and Pathways

• Alternative splicing •
• Bioengineering •
• Cellular memory •
• Epigenetics •
• Epigenetics •
• Eukaryotic regulatory networks •
• Gene expression •
• Hydrogen •
• Metabolism •
• mRNA export •
• mRNA splicing •
• Nuclear organization •
• Synthetic biology •
• Systems Biology •
• Tumor biology
•  

Cancer

• Epigenetics
•  

Metabolism; Metabolic Disease and Aging

• Energy •
• Metabolism
•  

Research Tools and Instrumentation

• Biofuel •
• Synthetic biology
•  

Therapeutic Discovery Tools and Assays

• Disease pathway modeling
•  

Therapeutics

• Chimeric proteins •
• Quantitatively designed proteins
•