Research ///
Synthetic biology is a multidisciplinary field that combines biology and engineering principles to generate new biological parts, modules, systems, and organisms. For example, synthetic promoters and engineered transcription factors can be used for the de-novo construction of artificial genetic circuits with well-defined functions. This approach provides powerful tools to overcome major challenges in a range of applications, such as basic research, biomedicine, ecology, agriculture, biosynthesis, and more. Our lab implements synthetic biology to develop practical biomedical applications, and to decipher human biology. Our versatile platforms could be implemented to treat a range of human diseases and to push forward pioneering research projects.
Synthetic gene circuits for cancer immunotherapy
We develop synthetic biology platforms to overcome major challenges in cancer immunotherapy, including the rarity of targetable tumor-specific antigens, tumor-mediated immune suppression, and the cytotoxicity caused by systemic immunomodulators administration. For example, we design and optimize synthetic gene circuits that precisely identify tumor-specific gene regulation patterns and generates the co-expression of multiple immunostimulatory outputs only from within cancer cells. Thus, the circuit selectively converts cancer cells into ‘Trojan horses’ that initiate a potent anti-tumor immune response, capable of significantly reducing tumor size in vivo and prolonged mouse survival. This approach has the potential to enable powerful new immunotherapies with higher efficiency and lower cytotoxicity and to study tumor immunology.
Synthetic promoters engineering
Cell-state specific promoters are useful for both basic and applicative research but are challenging to find. Synthetic promoters with enhanced cell-state specificity (SPECS) typically demonstrate superior specificity over native promoters, but their design is challenging, has a low success rate, and frequently requires gene regulation data that are not readily available. We recently developed a high-throughput SPECS library screening platform that could potentially provide de novo engineered SPECS to virtually any cell state and does not require any preliminary gene expression data. This platform was applied to discover promoters specific to sub-tissues of induced pluripotent stem cells (iPSCs) derived organoids, breast cancer, and glioma cancer stem cells.
COVID-19
Despite current global efforts, no anti-SARS-CoV-2 drug has yet become available. A major limitation in finding such drugs is the requirement to screen a myriad of molecules in the presence of a live SARS-CoV-2 virus, which requires extensive work in BL3 labs. We implement an integrated computational and synthetic biology platform that would enable focused, rapid and simple screen for anti-viral drugs with high therapeutic potential. By implementing designated computational and synthetic biology platforms we can screen in silico for selected molecules against SARS-CoV-2 infections. Our modular platform enables simple, rapid, and cost-effective screening of antiviral agents that can be implemented against a wide range of viruses.
In addition, we develop murine COVID-19 infection models, which could significantly support global research, for example, by enabling the assessment of anti-COVID-19 drugs in model systems. Mice do not express the COVID-19 receptor, hACE2, and therefore are immune to COVID-19 infection. We developed a protocol that enabled in vivo infection of mice lungs with viral vectors that generate hACE2 expression. This approach could potentially render mice susceptible to SARS-CoV-2 infection within a few days and therefore expand the currently limited availability of COVID-19 models.
