About the lab
The synthetic biology laboratory at the Department of Genetics and Morphology, University of Brasilia, DF, Brazil is currently interested on developing synthetic biology tools to regulate gene expression, and generate mutants that would allow for the investigation of several important biological questions in different organisms. Specifically, our laboratory is interested in using integrase-based genetic switches to investigate gene functionality . We are also using CRISPR-Cas9 suicide system and RNPs to develop multiplex tools to investigate genes related to virulence in Cryptococcus neoformans. https://www.synbiolab
Featured projects (1)
Although C. neoformans is a well-studied organism, there is still a lack of accurate repository of genetic parts for this organism and, therefore, this project aimed to build in silico a database describing marker promoters, terminators and coding sequences of selection, already tested and effective for C. neoformans.
Featured research (4)
As one of synthetic biology's foundations, biocircuits are a strategy of genetic parts assembling to recognize a signal and to produce a desirable output to interfere with a biological function. In this review, we revisited the progress in the biocircuits technology basis and its mandatory elements, such as the characterization and assembly of functional parts. Furthermore, for a successful implementation, the transcriptional control systems are a relevant point, and the computational tools help to predict the best combinations among the biological parts planned to be used to achieve the desirable phenotype. However, many challenges are involved in delivering and stabilizing the synthetic structures. Some research experiences, such as the golden crops, biosensors, and artificial photosynthetic structures, can indicate the positive and limiting aspects of the practice. Finally, we envision that the modulatory structural feature and the possibility of finer gene regulation through biocircuits can contribute to the complex design of synthetic chromosomes aiming to develop plants and algae with new or improved functions.
Cryptococcus neoformans is the etiologic agent of cryptococcosis, a lethal worldwide disease. Synthetic biology could contribute to its better understanding through engineering genetic networks. However, its major challenge is the requirement of accessible genetic parts. The database presented here provides 23 biological parts for this organism in Synthetic Biology Open Language.
Synthetic biology is a new area of science that operates at the intersection of engineering and biology and aims to design and synthesize living organisms and systems to perform new or improved functions. This novel biological area is considered of extreme relevance for the development of solutions to global problems. However, its teaching is often inaccessible to students, since many educational resources and methodological procedures are not available for understanding of complex molecular processes. On the other hand, digital fabrication tools, which allow the creation of 3D objects, are increasingly used for educational purposes, and several computational structures of molecular components commonly used in synthetic biology processes are deposited in open databases. Therefore, we hypothesize that the creation of biomolecular structures models by handling 3D physical objects using computer-assisted design (CAD) and additive fabrication based on 3D printing could help professors in synthetic biology teaching. In this sense, the present work describes the design and 3D print of the molecular models of the first synthetic genetic circuit, the toggle switch, which can be freely downloaded and used by teachers to facilitate the training of STEM students in synthetic biology.
Since the beginning of genetic engineering, the insertion of exogenous genes in host cells presented itself as an important challenge, which overtime augmented, either due to the increasing size of the inserts or to the requirement of precise target integration into the genome, demanding expression of the gene of interest and no interference with the endogenous genetic network of the targeted organism. With the advent of Synthetic Biology, there was an expansion from monogenic towards polygenic traits of interest leading to the requirement for the insertion of not only one or two genes, but entire metabolic pathways. Ultimately, it became clear the need for more refined studies of genomic organization, structuring and regulation. In order to avoid unstable gene expression and/or unpredictable phenotypes, many of these proposals required specific integration without modification of endogenous gene expression. A common approach to fulfill this challenge is to direct the inserts to intragenic or intergenic regions that allows the expression of the insert without changing the expression levels of local genes, called Genomic Safe Haven (GSH). One of the GSHs most commonly used in studies with human cells is the locus of the adeno-associated virus integration site 1 (AAVS1) in the PPP1R12C gene which, when targeted with transgenes, results in stable expression of the insert. For the same model organism, two other GSHs are also used, CCR5 and hROSA26, however all three are found in regions with high gene density and close to genes that are related to cancer. In order to expand the use of GSHs in different organisms and increase the number of intergenic GSHs, the Safe haven identification program (Ship) brings an optimized approach following defined criteria for refining the search for new insertion regions.
- Department of Genetics and Morphology
About Cíntia Marques Coelho
- Currently working on Synthetic Biology. Specifically designing and testing integrases-based genetic switches to control gene regulation in eukaryotic cells. Our laboratory is also interested on development of synthetic biology tools that can be applyied to study gene function on fungal research. We are evaluating suicidal CRISPR-Cas9 system and RNPs as a multiplex gene-editing tool in Crytococcus neoformans. Additionally we are development a software to identify Safe Harbour regions.