A team led by ETH Professor Yaakov Benenson has developed several new components for biological circuits. These components are key building blocks for constructing precisely functioning and programmable bio-computers.
Bio-engineers are working on the development of biological computers with the aim of designing small circuits made from biological material that can be integrated into cells to change their functions. In the future, such developments could enable cancer cells to be reprogrammed, thereby preventing them from dividing at an uncontrollable rate. Stem cells could likewise be reprogrammed into differentiated organ cells.
The researchers have not progressed that far yet. Although they have spent the past 20 years developing individual components and prototypes of biological computers, bio-computers today still differ significantly from their counterparts made of silicon, and bio-engineers still face several major obstacles.
A silicon chip, for example, computes with ones and zeros – current is either flowing or not – and it can switch between these states in the blink of an eye. In contrast, biological signals are less clear: in addition to ‘signal’ and ‘no signal’, there is a plethora of intermediate states with ‘a little bit of signal’. This is a particular disadvantage for bio-computer components that serve as sensors for specific biomolecules and transmit the relevant signal. Sometimes, they also send an output signal if no input signal is present, and the problem becomes worse when several such components are connected consecutively in a circuit.
ETH doctoral candidate Nicolas Lapique from the group led by Yaakov Benenson, Professor of Synthetic Biology in the Department of Biosystems Science and Engineering at ETH Zurich in Basel, has now developed a biological circuit that controls the activity of individual sensor components using internal "timer". This circuit prevents a sensor from being active when not required by the system; when required, it can be activated via a control signal. The researchers recently published their work in the scientific journal Nature Chemical Biology.
To understand the underlying technology, it is important to know that these biological sensors consist of synthetic genes that are read by enzymes and converted into RNA and proteins. In the controllable biosensor developed by Lapique, the gene responsible for the output signal is not active in its basic state, as it is installed in the wrong orientation in the circuit DNA. The gene is activated via a special enzyme, a recombinase, which extracts the gene from the circuit DNA and reinstalls it in the correct orientation, making it active. “The input signals can be transmitted much more accurately than before thanks to the precise control over timing in the circuit,” says Benenson.
To date, the researchers have tested the function of their activation-ready sensor in cell culture of human kidney and cancer cells. Nevertheless, they are already looking ahead to further developing the sensor so that it can be used in a more complex bio-computer that detects and kills cancer cells. These bio-computers will be designed to detect typical cancer molecules. If cancer markers are found in a cell, the circuit could, for example, activate a cellular suicide programme. Healthy cells without cancer markers would remain unaffected by this process.
Still, combining various biological components to form more complex bio-computers constitutes a further challenge for bio-engineers. “In electronics, the different components that make up a circuit are always connected in the same way: with a wire through which the current either flows or not,” explains Benenson. In biology, there are a variety of different signals – a host of different proteins or microRNA molecules. In order to combine biologic components in any desired sequence signal converters must be connected between them.
Laura Prochazka, also a doctoral candidate student under Benenson, has developed a versatile signal converter. She published her work recently in the magazine Nature Communications. A special feature of the new component is that not only it converts one signal into another, but it can also be used to convert multiple input signals into multiple output signals in a straightforward manner.
This new biological platform will significantly increase the number of applications for biological circuits. As Benenson says, “The ability to combine biological components at will in a modular, plug-and-play fashion means that we now approach the stage when the concept of programming as we know it from software engineering can be applied to biological computers. Bio-engineers will literally be able to program in future.”
Lapique N, Benenson Y: Digital switching in a biosensor circuit via programmable timing of gene availability. Nature Chemical Biology, online publication 14 October 2014, doi: 10.1038/nchembio.1680
Prochazka L, Angelici B, Häfliger B, Benenson Y: Highly modular bow-tie gene circuits with programmable dynamic behavior, Nature Communications, online publication 14 October 2014, doi: 10.1038/ncomms5729
Yaakov Benenson | Eurek Alert!
Single mutation dramatically changes structure and function of bacteria's transporter proteins
23.10.2019 | New York University
Bacterial lifestyle alters the evolution of antibiotic resistance
23.10.2019 | University of Pittsburgh
After first reporting the existence of quantum knots, Aalto University & Amherst College researchers now report how the knots behave
A quantum gas can be tied into knots using magnetic fields. Our researchers were the first to produce these knots as part of a collaboration between Aalto...
Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.
Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...
A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)
It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
23.10.2019 | Materials Sciences
23.10.2019 | Physics and Astronomy
23.10.2019 | Medical Engineering