Kirill Sechkar
@ksechkar.bsky.social
DPhil Engineering Science student at Oxford Uni. All opinions are my own, but the risk you take by reading them is yours
Other soc. media: http://cosoc.com/KSechkar
Other soc. media: http://cosoc.com/KSechkar
Thrilled to have attended this week's iGEM Jamboree - full of amazing teams, brilliant research and indomitable SynBio optimisim
But even if you couldn't come, you can still watch me embarass myself by trying to write it up as a satirical sketch (link in the next post)
But even if you couldn't come, you can still watch me embarass myself by trying to write it up as a satirical sketch (link in the next post)
November 1, 2025 at 11:30 AM
Thrilled to have attended this week's iGEM Jamboree - full of amazing teams, brilliant research and indomitable SynBio optimisim
But even if you couldn't come, you can still watch me embarass myself by trying to write it up as a satirical sketch (link in the next post)
But even if you couldn't come, you can still watch me embarass myself by trying to write it up as a satirical sketch (link in the next post)
We successfully simulate our protocol using different models of various complexities (e.g. see results for a mechanistic resource-aware cell model in the pic below) – gives us reason to think it should work in (even more complex) real cells! 7/
April 4, 2025 at 9:22 AM
We successfully simulate our protocol using different models of various complexities (e.g. see results for a mechanistic resource-aware cell model in the pic below) – gives us reason to think it should work in (even more complex) real cells! 7/
From start to finish, our proposed method involves first establishing the probe’s properties, then using it to do CBC with the genetic module of interest. The results can then predict how any two characterised modules will compete for resources! 6/
April 4, 2025 at 9:22 AM
From start to finish, our proposed method involves first establishing the probe’s properties, then using it to do CBC with the genetic module of interest. The results can then predict how any two characterised modules will compete for resources! 6/
Here, the module of interest’s output is its fluorescent gene expression, and the feedback input is e.g. chemical induction of another ‘probe’ genetic module competing with it for resources 5/
April 4, 2025 at 9:22 AM
Here, the module of interest’s output is its fluorescent gene expression, and the feedback input is e.g. chemical induction of another ‘probe’ genetic module competing with it for resources 5/
To gauge resource demands, we often look at how modules compete for gene expression resources with constitutive fluorescent reporter genes. But there’s a problem: in multistable systems, constant resource competition may drive your system to just one steady state among many possible
April 4, 2025 at 9:22 AM
To gauge resource demands, we often look at how modules compete for gene expression resources with constitutive fluorescent reporter genes. But there’s a problem: in multistable systems, constant resource competition may drive your system to just one steady state among many possible
NEW PREPRINT! Do you think we can do better when characterising resource competition properties of gene circuit modules? If no, think again; if yes, you’re in for a pitch how exactly we can do that – automated culturing, cybergenetic control and all! 1/
doi.org/10.1101/2025...
doi.org/10.1101/2025...
April 4, 2025 at 9:22 AM
NEW PREPRINT! Do you think we can do better when characterising resource competition properties of gene circuit modules? If no, think again; if yes, you’re in for a pitch how exactly we can do that – automated culturing, cybergenetic control and all! 1/
doi.org/10.1101/2025...
doi.org/10.1101/2025...
We also consider beneficial *native* gene mutations. For the same growth advantage, these are less prone to triggering the Punisher than synthetic gene loss, yielding better fitness. Clonal interference can thus help to hinder engineered cell populations’ function loss 9/10
February 12, 2025 at 12:53 PM
We also consider beneficial *native* gene mutations. For the same growth advantage, these are less prone to triggering the Punisher than synthetic gene loss, yielding better fitness. Clonal interference can thus help to hinder engineered cell populations’ function loss 9/10
How about transient reductions in burden due to uneven plasmid and cell cycle fluctuations? We can likewise model these to show that the Punisher is robust to such disturbances 8/10
February 12, 2025 at 12:53 PM
How about transient reductions in burden due to uneven plasmid and cell cycle fluctuations? We can likewise model these to show that the Punisher is robust to such disturbances 8/10
Though the Punisher’s aimed at penalising mutations of genes burdening the cell primarily via resource competition, we also model metabolic burden. Turns out, our design can punish mutations of metabolically burdensome genes, too – just tune the chemical induction again! 7/10
February 12, 2025 at 12:53 PM
Though the Punisher’s aimed at penalising mutations of genes burdening the cell primarily via resource competition, we also model metabolic burden. Turns out, our design can punish mutations of metabolically burdensome genes, too – just tune the chemical induction again! 7/10
We also define a population model based on deterministic and stochastic simulations, directly linking physiological parameters of synthetic genes and circuit performance on a populational level. Our model shows the Punisher really is helpful in settings like bioreactors 5/10
February 12, 2025 at 12:53 PM
We also define a population model based on deterministic and stochastic simulations, directly linking physiological parameters of synthetic genes and circuit performance on a populational level. Our model shows the Punisher really is helpful in settings like bioreactors 5/10
Direct sensing of burden gives the Punisher an edge over extant designs (like co-expression of essential genes with synthetic genes of interest), which may accidentally encourage mutant cell growth through unintended responses 4/10
February 12, 2025 at 12:53 PM
Direct sensing of burden gives the Punisher an edge over extant designs (like co-expression of essential genes with synthetic genes of interest), which may accidentally encourage mutant cell growth through unintended responses 4/10
Thanks to a self-activating switch, the Punisher’s triggered by burden reduction (eg by mutations) and excises an essential gene. The switching threshold can be tuned by chemical induction, so it can be reused for many applications without any long & costly DNA engineering 3/10
February 12, 2025 at 12:53 PM
Thanks to a self-activating switch, the Punisher’s triggered by burden reduction (eg by mutations) and excises an essential gene. The switching threshold can be tuned by chemical induction, so it can be reused for many applications without any long & costly DNA engineering 3/10
Our paper on countering mutations in engineered cell populations has now been published with @royalsocietypublishing.org ! Come for our biomolecular controller that mitigates mutation spread, stay for resource-aware gene circuit design and modelling tools 1/10
doi.org/10.1098/rsif.2024.0602
doi.org/10.1098/rsif.2024.0602
February 12, 2025 at 12:53 PM
Our paper on countering mutations in engineered cell populations has now been published with @royalsocietypublishing.org ! Come for our biomolecular controller that mitigates mutation spread, stay for resource-aware gene circuit design and modelling tools 1/10
doi.org/10.1098/rsif.2024.0602
doi.org/10.1098/rsif.2024.0602
...and that's it for today! (though a digest of *some* #SBUK2024 posters may follow later)
Huge thanks to the organisers @engbioirc.bsky.social , to everyone who presented, and to you all for following my live(ish) report!
14/14
Huge thanks to the organisers @engbioirc.bsky.social , to everyone who presented, and to you all for following my live(ish) report!
14/14
November 28, 2024 at 5:53 PM
...and that's it for today! (though a digest of *some* #SBUK2024 posters may follow later)
Huge thanks to the organisers @engbioirc.bsky.social , to everyone who presented, and to you all for following my live(ish) report!
14/14
Huge thanks to the organisers @engbioirc.bsky.social , to everyone who presented, and to you all for following my live(ish) report!
14/14
Meantime, our lab's Scott Stacey presents sponge RNAs - an underexplored biocontrol mechanism which lets reduce noise, control expression quickly, and achieve coupled gene regulation...
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November 28, 2024 at 10:28 AM
Meantime, our lab's Scott Stacey presents sponge RNAs - an underexplored biocontrol mechanism which lets reduce noise, control expression quickly, and achieve coupled gene regulation...
4/
4/
My supervisor Prof Harrison Steel explains how and why we use #control in SynBio. For one, it makes directed evo more efficient by observing & steering *very many* *individual* cells with microfluidics! Works really well if you're selecting for growth-uncorrelated traits
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2/
November 28, 2024 at 10:01 AM
My supervisor Prof Harrison Steel explains how and why we use #control in SynBio. For one, it makes directed evo more efficient by observing & steering *very many* *individual* cells with microfluidics! Works really well if you're selecting for growth-uncorrelated traits
2/
2/
The summaries will continue, but after the poster session - which includes yours truly at stall 67 with an *all-new* project on experimentally investigating non-modularity in gene circuits caused by resource competition 6/
November 27, 2024 at 5:33 PM
The summaries will continue, but after the poster session - which includes yours truly at stall 67 with an *all-new* project on experimentally investigating non-modularity in gene circuits caused by resource competition 6/
Starting off with Synthetic Cells and why we need them (prototyping life, doing logic and more - that's why)
Among other things, a very creative way to make artificial cells divide controllably by ligand binding of membranes 2/
Among other things, a very creative way to make artificial cells divide controllably by ligand binding of membranes 2/
November 27, 2024 at 11:30 AM
Starting off with Synthetic Cells and why we need them (prototyping life, doing logic and more - that's why)
Among other things, a very creative way to make artificial cells divide controllably by ligand binding of membranes 2/
Among other things, a very creative way to make artificial cells divide controllably by ligand binding of membranes 2/
#SBUK2024 is about to begin! Let's see what exciting new research the next two days have in store... #BiochemEvent 1/many
November 27, 2024 at 10:41 AM
#SBUK2024 is about to begin! Let's see what exciting new research the next two days have in store... #BiochemEvent 1/many