Synthetic biology is an emergent scientific field offering new prospects for the future and exhibiting broad applications in many industrial sectors including the chemical, food, medical, and agricultural industries. Applications include the production of biofuels, added-value chemicals, food flavors, drugs, synthetic vaccines, and biosensors. Moreover, it can be used as a tool for bioremediation or in in vivo or in vitro health applications. In our Synthetic Biology group five main research topics are being developed.
Other Group Research Labs
The BIOSYSTEMS carries out research in Synthetic Biology
Main Topics of the Research Team
Discovery of new enzymes or bioproducts using synthetic biology strategies
Biosynthetic pathways frequently use enzymes with activities well-below the expected levels. For example, the effective conversion of lignocellulose by a sustainable process is currently incomplete and there is a need to find novel and robust catalysts to overcome this fact. Our group is using function-based metagenomic approaches to identify novel lignocellulose-degrading enzymes (e.g. cellulases, xylanases and laccases) present in compost samples. Moreover, this strategy is also being used for the identification of novel biosurfactants (and genes) from microorganisms inhabiting oil polluted environments. The identification of novel biosurfactants will greatly contribute to expand their market and applications in different industries.
Synthetic biology approaches for engineering new pathways, functions and organisms
Synthetic biology intersects directly with metabolic engineering regarding the use of enzymes as interchangeable parts for constructing or reconstructing metabolic pathways to increase productivity, but also to produce high-value compounds in a cheap, efficient, and clean way. Our group is focused in applying synthetic biology strategies for engineering new pathways in model organisms such as Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis, Zymomonas mobilis, Pseudomonas aeruginosa, among others. The main purpose is to obtain organisms with new and/or improved functions towards the production of added-value products (e.g. curcuminoids, furanocoumarins, acrylic acid, fructooligosaccharides, xylooligosaccharides, lactulose, rhamnolipids, biosurfactants, and chondroitin). These approaches involve the use of engineering principles that use modular genetic parts to design and engineer regulatory circuits to control gene expression in response to intracellular metabolic states for the improved production of a given compound in model organisms. Also, several modeling and engineering steps are being used to program organisms to execute new synthetic pathways for the production of interest compounds triggered by external stimulus (e.g. temperature). The biosynthetic parts or pathways are being tested using DNA vectors or inserted in the genome using genome editing techniques such as CRISPR-Cas9. In addition, protoplast fusion is being used to construct engineered microbial strains with desired properties by combining genomes from different microorganisms. Those strains will be used in ongoing Microbial Enhanced Oil Recovery (MEOR) projects.
Synthetic biology in the triple negative breast cancer diagnosis and treatment
Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic subtype of breast cancer that lacks the expression of estrogen receptors, progesterone receptors, and amplification of the human epidermal growth factor receptor 2 (HER2). Consequently, this type of cancer does not respond to hormonal therapy medicines or medicines that target HER2 protein receptors. Therefore, the development of novel targeted drug delivery therapies is essential for a correct and timely intervention in TNBC patients. Our group is focused in the development of platforms for TNBC diagnosis and treatment. Exosomes are being engineered to carry siRNAs for dual targeting of two specific pathways involved in TNBC: MAPK and Pi3K/Akt/mTOR. Phage display, SELEX and cell-SELEX techniques are being used to identify cancer biomarkers (peptide, DNA sequences, aptamers) to target TNBC and monitoring it in a point-of-care (e.g. test-strip) device. Genome editing tools such as CRISPR-Cas9 are also being applied in mammalian cells to modulate microRNAs involved in the PTEN/AKT/FOXO3 pathway, which usually exhibits genomic abnormalities in TNBC cells.
Synthetic biology sensors
Biomarkers are recognition molecules widely defined as indicators of a biological state. Therefore, the identification of novel biomarkers can lead to the precocious detection and treatment of some diseases. Aptamers are short single-stranded RNA and DNA oligonucleotides that can specifically recognize and tightly bind with high affinity a broad variety of targets ranging from small ions, single molecules to proteins, and even whole cells. Our research group is dedicated to study and identify new aptamers that allow to select specific targets using different technologies. SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology is used for the selection of full-length aptamers with unique properties from very large random sequence oligonucleotide libraries. Cell-SELEX, a SELEX variant, uses whole living cells as targets for aptamer selection based on differences at the molecular level between cell lines. Other techniques such as Phage Display screening are also used to identify high-affinity peptides that selectively recognize molecular markers. This technique allows taking advantage of the extensive genetic flexibility of bacteriophages to create a variety of modifications on their surface and allows to screen extensive random peptide libraries.
Using synthetic biology approaches to study bacterial adhesion onto biological and non-biological surfaces
Pathogen infections are a health concern worldwide since some diseases that were controlled in the past are reemerging due to the increased bacterial resistance to antibiotics. Therefore, alternative or complementary strategies to antibiotics ought to be developed. Additionally, actual diagnostic methods involve complex and lengthy procedures. Our group, as a partner in Viral and Bacterial Adhesin Network Training (ViBrANT), is working on the design of novel solutions that can capture/enrich pathogens from clinical samples. This will be of utmost relevance for clinical diagnostics and also to direct treatment to a specific pathogen instead of killing essential gut flora. Specific ligands (peptides/proteins, biosurfactants and aptamers) that bind to the extracellular matrix, membrane components or capsids of pathogens will be immobilized onto the surface of materials than can be further used for fabrication of diagnostic devices. Non-pathogenic strains of E. coli are being engineered to express adhesin genes from certain bacterial pathogens using Gibson assembly cloning. These engineered E. coli strains will mimic the pathogenic strains and will be further used to test and select immobilized ligands.