Browsing by Subject "Genetic circuits"

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Open Access
Engineered bacteria with genetic circuits accumulating nanomagnets as MRI contrast agents
(Wiley, 2022-01-25) Yavuz, Merve; Ütkür, Mustafa; Kehribar, Ebru Şahin; Yağız, Ecrin; Sarıtaş, Emine Ülkü; Şeker, Urartu Özgür Şafak
The demand for highly efficient cancer diagnostic tools increases alongside the high cancer incidence nowadays. Moreover, there is an imperative need for novel cancer treatment therapies that lack the side effects of conventional treatment options. Developments in this aspect employ magnetic nanoparticles (MNPs) for biomedical applications due to their stability, biocompatibility, and magnetic properties. Certain organisms, including many bacteria, can synthesize magnetic nanocrystals, which help their spatial orientation and survival by sensing the earth's geomagnetic field. This work aims to convert Escherichia coli to accumulate magnetite, which can further be coupled with drug delivery modules. The authors design magnetite accumulating bacterial machines using genetic circuitries hiring Mms6 with iron-binding activity and essential in magnetite crystal formation. The work demonstrates that the combinatorial effect of Mms6 with ferroxidase, iron transporter protein, and material binding peptide enhances the paramagnetic behavior of the cells in magnetic resonance imaging (MRI) measurements. Cellular machines are also engineered to display Mms6 peptide on the cell surface via an autotransporter protein that shows augmented MRI performance. The findings are promising for endowing a probiotic bacterium, able to accumulate magnetite intracellularly or extracellularly, serving as a theranostics agent for cancer diagnostics via MRI scanning and hyperthermia treatment. © 2022 Wiley-VCH GmbH.
Open Access
Genetic logic gates enable patterning of amyloid nanofibers
(WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, 2019) Kalyoncu, Ebuzer; Ahan, Recep Erdem; Özçelik, Cemile Elif; Şeker, Urartu Özgür Şafak
Distinct spatial patterning of naturally produced materials is observed in many cellular structures and even among communities of microorganisms. Reoccurrence of spatially organized materials in all branches of life is clear proof that organization is beneficial for survival. Indeed, organisms can trick the evolutionary process by using organized materials in ways that can help the organism to avoid unexpected conditions. To expand the toolbox for synthesizing patterned living materials, Boolean type “AND” and “OR” control of curli fibers expression is demonstrated using recombinases. Logic gates are designed to activate the production of curli fibers. The gates can be used to record the presence of input molecules and give output as CsgA expression. Two different curli fibers (CsgA and CsgA‐His‐tag) production are then selectively activated to explore distribution of monomers upon coexpression. To keep track of the composition of fibers, CsgA‐His‐tag proteins are labeled with nickel–nitrilotriacetic acid (Ni–NTA‐) conjugated gold nanoparticles. It is observed that an organized living material can be obtained upon inducing the coexpression of different CsgA fibers. It is foreseen that living materials with user‐defined curli composition hold great potential for the development of living materials for many biomedical applications.
Open Access
Synthetic genetic circuits for self-actuated cellular nanomaterial fabrication devices
(American Chemical Society, 2019) Ölmez, Tolga Tarkan; Şahin-Kehribar, Ebru; Işılak, Musa Efe; Lu, T. K.; Şeker, Urartu Özgür Şafak
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.