An increasing interest in building novel biological devices with designed cellular functionalities has triggered the search of innovative tools for biocomputation. Utilizing the tools of synthetic biology, numerous genetic circuits have been implemented such as engineered logic operation in analog and digital circuits. Whole cell biosensors are widely used biological devices that employ several biocomputation tools to program cells for desired functions. Up to the present date, a wide range of whole-cell biosensors have been designed and implemented for disease theranostics, biomedical applications, and environmental monitoring. In this review, we investigated the recent developments in biocomputation tools such as analog, digital, and mix circuits, logic gates, switches, and state machines. Additionally, we stated the novel applications of biological devices with computing functionalities for diagnosis and therapy of various diseases such as infections, cancer, or metabolic diseases, as well as the detection of environmental pollutants such as heavy metals or organic toxic compounds. Current whole-cell biosensors are innovative alternatives to classical biosensors; however, there is still a need to advance decision making capabilities by developing novel biocomputing devices.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently a global pandemic with unprecedented public health, economic and social impact. The development of effective mitigation strategies, therapeutics and vaccines relies on detailed genomic and biological characterization of the regional viruses. This study was carried out to isolate SARS-CoV-2 viruses circulating in Anatolia, and to investigate virus propagation in frequently-used cells and experimental animals. We obtained two SARS-CoV-2 viruses from nasopharngeal swabs of confirmed cases in Vero E6 cells, visualized the virions using atomic force and scanning electron microscopy and determined size distribution of the particles. Viral cytopathic effects on Vero E6 cells were initially observed at 72 h post-inoculation and reached 90% of the cells on the 5th day. The isolates displayed with similar infectivity titers, time course and infectious progeny yields. Genome sequencing revealed the viruses to be well-conserved, with less than 1% diversity compared to the prototype virus. The analysis of the viral genomes, along with the available 62 complete genomes from Anatolia, showed limited diversity (up to 0.2% on deduced amino acids) and no evidence of recombination. The most prominent sequence variation was observed on the spike protein, resulting in the substitution D614G, with a prevalence of 56.2%. The isolates produced non-fatal infection in the transgenic type I interferon knockout (IFNAR −/- ) mice, with varying neutralizing antibody titers. Hyperemia, regional consolidation and subpleural air accumulation was observed on necropsy, with similar histopathological and immunohistochemistry findings in the lungs, heart, stomach, intestines, liver, spleen and kidneys. Peak viral loads were detected in the lungs, with virus RNA present in the kidneys, jejunum, liver, spleen and heart. In conclusion, we characterized two local isolates, investigated in vitro growth dynamics in Vero E6 cells and identified IFNAR−/− mice as a potential animal model for SARS-CoV-2 experiments.

The COVID-19 (coronavirus disease-19) pandemic affected more than 180 million people around the globe, causing more than five million deaths as of January 2022. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing; however, prophylactic drugs are highly demanded to ensure secure social contact. A number of drug molecules have been repurposed to fight against SARS-CoV-2, and some of them have been proven to be effective in preventing hospitalization or ICU admissions. Here, we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of SARS-CoV-2 and its variants, Delta and Omicron, into the Vero E6 cell lines and IFNAR –/– mouse models by attaching to the spike protein of SARS-CoV-2. Given the current mutation frequency of SARS-CoV-2, we believe that GRFT protein-based drugs will have a high impact in preventing the transmission of both the Wuhan strain as well as any other emerging variants, including Delta and Omicron variants, causing the high-speed spread of COVID-19.

SARS-CoV-2 is a human pathogen and the main cause of COVID-19 disease, announced as a global pandemic by the World Health Organization. COVID-19 is characterized by severe conditions, and early diagnosis can make dramatic changes for both personal and public health. Low-cost, easy-to-use diagnostic capabilities can have a very critical role in controlling the transmission of the disease. Here, we are reporting a state-of-the-art diagnostic tool developed with an in vitro synthetic biology approach by employing engineered de novo riboregulators. Our design coupled with a home-made point-of-care device can detect and report the presence of SARS-CoV-2-specific genes. The presence of SARS-CoV-2-related genes triggers the translation of sfGFP mRNAs, resulting in a green fluorescence output. The approach proposed here has the potential of being a game changer in SARS-CoV-2 diagnostics by providing an easy-to-run, low-cost diagnostic capability.

Genetically controlled synthetic biosystems are being developed to create nanoscale materials. These biosystems are modeled on the natural ability of living cells to synthesize materials: many organisms have dedicated proteins that synthesize a wide range of hard tissues and solid materials, such as nanomagnets and biosilica. We designed an autonomous living material synthesizing system consisting of engineered cells with genetic circuits that synthesize nanomaterials. The circuits encode a nanomaterial precursor-sensing module (sensor) coupled with a materials synthesis module. The sensor detects the presence of cadmium, gold, or iron ions, and this detection triggers the synthesis of the related nanomaterial-nucleating extracellular matrix. We demonstrate that when engineered cells sense the availability of a precursor ion, they express the corresponding extracellular matrix to form the nanomaterials. This proof-of-concept study shows that endowing cells with synthetic genetic circuits enables nanomaterial synthesis and has the potential to be extended to the synthesis of a variety of nanomaterials and biomaterials using a green approach.

Glycosylation is a crucial post-translational modification for a wide range of functionalities. Adhesive protein-based biomaterials in nature rely on heavily glycosylated proteins such as spider silk and mussel adhesive proteins....

Hydroxyapatite (HAP) is the major biomineral of bone. Despite the large number of studies addressing HAP formation, a fundamental understanding of the critical roles of HAP-forming proteins in vitro is needed. Effects of two HAP-interacting proteins, osteocalcin (OCN) and osteopontin (OPN), on HAP formation was investigated via in vitro biomineralization experiments, and their outcomes on the crystal structure of calcium phosphate (CaP) was revealed. Our data suggest that OCN concentration is negatively correlated with crystal formation rate and crystal size, yet the presence of OCN leads to a more ordered HAP crystal formation. On the other hand, OPN protein promotes faster formation of CaP crystals potentially working as a growth site for mineral formation, and it decreases the Ca:P ratio. This effect results in a shift from HAP-type minerals to less ordered crystals. The crystal size, shape, and Ca:P ratio can be tuned to design improved mammalian hard tissue environment-mimicking matrices by taking advantage of the OCN and OPN proteins on crystal formation. We believe our current findings will lead to innovative approaches for bone biomineralization in regenerative medicine.

The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is continuously infecting people all around the world since its outbreak in 2019. Studies for numerous infection detection strategies are continuing. The sensitivity of detection methods is crucial to separate people with mild infections from people who are asymptomatic. In this sense, a strategy that would help to capture and isolate the SARS‐CoV‐2 virus prior to tests can be effective and beneficial. To this extent, genetically engineered biomaterials grounding from the biofilm protein of Escherichia coli are beneficial due to their robustness and adaptability to various application areas. Through functionalizing the E. coli biofilm protein, diverse properties can be attained such as enzyme display, nanoparticle production, and medical implant structures. Here, E. coli species are employed to express major curli protein CsgA and Griffithsin (GRFT) as fusion proteins, through a complex formation using SpyTag and SpyCatcher domains. In this study, a complex system with a CsgA scaffold harboring the affinity of GRFT against Spike protein to capture and isolate SARS‐CoV‐2 virus is successfully developed. It is shown that the hybrid recombinant protein can dramatically increase the sensitivity of currently available lateral flow assays for Sars‐CoV‐2 diagnostics.