Just published: "Inteins: A Swiss Army Knife for #SyntheticBiology" with @St_Anastassov & @KhammashLab in Biotechnology Advances. One day, #Inteins 𝐜𝐨𝐮𝐥𝐝 make #genetic circuit design as simple as electric ones! 🧬⚡ https://t.co/en8cziEXTi

We have crafted 3 different topologies that implement various anti-windup strategies. We developed a couple of theorems that link this molecular strategies to well-known control-theoretic strategies. We also devised reaction network and genetic realizations using inteins.

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An anti-windup strategy is like a therapeutic intervention, helping a controller to move past its traumatic experience by promoting a form of forgetfulness toward the disruptive event. Anti-windup circuits thus avoid windup-induced instabilities and poor dynamic performance. 2/n

Check out our paper in the @KhammashLab on #biomolecular protection circuits. Integral windup is similar to a trauma inflicted by severe disturbances with lasting effects even after the disturbance ends. How do we mitigate that in biomolecular circuits?1/n https://t.co/7F3S8ov380

My favorite illustration of how geometric intuition fails miserably in high dimensions.

One of the highlights of 2023 is teaching #controlsystems to an incredible cohort at @Ashesi University in #ghana 🇬🇭 as part of the @ETH4D (ETH for Development) master program. It was an absolute pleasure getting to know all of the students!

Are you looking for a versatile and inexpensive illumination platform for optogenetics experiments? Check out our new DIYA device... It's become the most popular platform in our lab for bacterial, yeast and mammalian optogenetics. #synbio #optogenetics https://t.co/txk715XLFH

Reference-based antithetic integral feedback (AIF) was previously shown to deliver robust perfect adaptation at the population level, but may increase cell-to-cell variability. The sensor-based AIF, however, is capable of reducing variability, thanks to precisely the hidden P!

Actuating by the sensor molecule Z2 (instead of Z1) embeds a (filtered) PI controller in just one actuation reaction. This brings with it the enhanced dynamic performance offered by the P component while maintaining the robustness offered by the integrator.

Check out our latest preprint in the @KhammashLab on "A Hidden Proportional Feedback Mechanism Underlies Enhanced Dynamic Performance and Noise Rejection in Sensor-Based Antithetic Integral Control" https://t.co/LdzOQZg8Pi Special thanks to my coauthor @MucunHou

Fast post-translational modifications performed by inteins may generate sophisticated #controllers. To study and untangle the underlying dynamics, we have developed two theorems that enable a graphical screening for #RPA and a #modelreduction recipe accessible to non-experts 5/5

Multiple #genetic #circuits, with remarkable dynamic ranges, were designed, built and tested. This versatility was possible because with split inteins you can convert any protein to a controller molecule thanks to their small size, flexibility and modularity 4/5

Achieving such property has important implications in many fields such as #metabolic #engineering, #bioproduction and #celltherapy. But how can we embed reliable RPA-achieving controllers as molecules inside the cells? Short answer: Close the feedback loop with split inteins 3/5

#Homeostasis is a recurring theme in #biology endowing the cells with a remarkable property which makes them resilient to noisy/uncertain environments. A similar, but more stringent, notion is #Robust Perfect Adaptation which is achievable with #integral #feedback #control 2/5

Check out our work in the @KhammashLab on building #integral controllers genetically with split #inteins! (Play the video with sound on for an animation of a genetic circuit!) https://t.co/peQ2H3TrmH Special thanks to my coauthors @St_Anastassov, @Ch_Hs_Chang & @KhammashLab 1/5

Various designs of Biomolecular Proportional-Integral-Derivative (PID) controllers have been proposed. On top of homeostatic properties, these advanced controllers enhance the performance in both the deterministic and stochastic setting. They remain to be built! 4/3

Biomolecular Integral Controllers, with their remarkable homeostatic properties, are already designed and even built and tested across various cell types. 3/3

Synthetic negative-feedback circuits have already found their way into exciting applications ranging from metabolic engineering to cell population control to cell therapy. 2/3

How are feedback controllers built with molecules? Check out our @KhammashLab review paper on "Biomolecular Feedback Controllers: From Theory to Applications" published in Current Opinion in Biotechnology! 1/3 Special thanks to my co-author @Ch_Hs_Chang. https://t.co/fi8ZqAZWGR

How do biological networks maintain tight regulation of variables while being subjected to an onslaught of perturbations? We establish simple universal principles for maximal robust adaptation in all biomolecular systems. https://t.co/8YSa47ohtS #sysbio #synbio #cybergenetics