Tom Ellis
@proftomellis
Synthetic Biology & Synthetic Genomics @ Imperial College London and the Sanger Institute. Bilingual in English and DNA. Views are either my own or my microbes'
And the minimal sets of genes that can function reasonably well in lots of growth conditions is a much narrower number than in just standard growth media. An unsurprising but cautionary result for future work in genome minimisation.
But perhaps the most interesting result is looking at the robustness. Our yeast can grow relatively well in standard conditions when half of the gene content for cell cycle control is removed. But the same yeast fail badly when moved into more stressful conditions.
Anastasiya then isolated and sequenced 25 of these ‘minimised sets’ from the experiment and found gene combinations that had lost multiple cyclin and regulator genes but still grew well in several conditions. Excitingly these sets matched predicted minimal models from Matteo.
POLAR-seq revealed hundreds of different deletion combinations present in the pool of yeast cells after recombination, but the vast majority of cells that were growing contained a narrower set - presumably the fitter possibilities.
Inducing Cre recombinase in a growing population of yeast cells containing this synthetic genome module led to a huge change in the gene content of the synthetic module in the yeast cells, with bulk sequencing showing which genes are happy to be lost and which need to stay.
Once we got to healthy yeast with a synthetic genome module with 6 of the 9 cyclins and the 3 regulators in place, we decided to start the combinatorial work. Theoretically 512 different deletion sets can be made from combinatorial deletion from this 9 gene cluster.
This was some hardcore genome engineering as we wanted to keep gene sequences identical to wildtype and we were deleting and reinserting genes that are quite important for the cell to be healthy enough to engineer. Anastasiya pushed the boundaries with CRISPR in yeast to do it.
So with Matteo Barberis’ guidance, Anastasiya targeted 3 regulators (Sic1 and Forkhead 1 & 2) and as many cyclin genes as possible and relocated these genes and their flanking regulatory DNA into a synthetic cluster - a module with LoxP recombination sites between each gene.
5 days left now to apply for the postdoc opportunity in my lab at Imperial in London 🇬🇧 - there’s a chance that we can hire 2 people into the team on this synthetic biology and materials theme. Application link is here - www.imperial.ac.uk/jobs/search-...
Excited to have Volker Sieber from TU Munich and others join me in Thailand for the 2026 SynBio/Biocatalysis Symposium at Vidyasirimedhi Institute of Science and Technology (VISTEC) 🇹🇭 Thanks to Pimchai Chaiyen and her team for organising these two days of cutting edge science and good food.
Overall we found genetic engineering and coculturing strategies possible in all strains, but with some being better than others. No single strain wins out as best for everything which is a shame, but future strain engineering may change this. Watch this space. 👀
And in a final bit of fun, they then showed how different engineered strains of BC-producing bacteria can weld their materials together in a patchwork form to create some interesting looking materials.
Stacey and Katie then went further and tested how the different bacteria can co-culture with engineered E.coli cells and engineered yeast cells, testing at different temperatures and assessing all sorts of metrics.
Stacey, Katie and Maria tested out genetic engineering using a modular SynBio toolkit (KTK) in 4 widely-used species of Komagataeibacter and compared successes and failures.
His PhD project has been great fun to co-supervise and a paper is on its way soon. The move of the Nakayama lab to OIST means this work will be continued in Okinawa 🇯🇵 too, despite Oli himself moving on to new exciting plant-based things.
Oli explored how the Auxin-mediated patterning system common to plants could be engineered into yeast strains to push the tools for multicellular pattern formation in everyone’s favourite food fungus.
Congratulations to Dr Oliver Hernandez Fernandez who passed his PhD viva exam on Friday after 4 years at Imperial co-supervised by myself, Naomi Nakayama and Vahid Shahrezaei.
Great talk today at VISTEC from Thapakorn Jaroentomeechai whose setting up his SynGlyco Lab at Mahidol University in Bangkok 🇹🇭 - great use of synbio and cell-free systems to study and apply glycobiolgy.
Today marks my first day at VISTEC in Rayong 🇹🇭 - warm hosts for my sabbatical in Thailand 🙏🏻 My family and I will be spending time here and Bangkok over the next 8 months making connections and collaborations in synthetic biology and living materials work.
Join us and these amazing speakers next March'26 at Synthetic Biology for Health and Sustainability - an international conference held at the Wellcome Genome campus near Cambridge UK. Abstracts deadline: December 1st, 2025 Register here - x.com/gallowaylabm...
Was interesting to hear today about the annual “SynBio Challenges” competition that has got going in China as a cheaper/free alternative to iGEM - m.synbiochallenges.com/application/...
DISCARD - The aim is to combine gene segments to create a new genome, but recombination events will cause localised or system-wide death.
A new review paper from our lab courtesy of @jazzsynbio.bsky.social is published in Trends in Biotechnology In this review, we look at the many opportunities for synthetic biology to be used in the research and applications of Holobionts.
Yesterday was the first day of autumn and guess what appeared in the window of the Peninsula hotel in London.
It's been great to see this work develop under Stacey's expertise in our lab and so glad that it's finally out. Klaudia Ciurkot played a big role in applying the POLAR-Seq part so is an author too. We also thank Wolfgang Ott for the ELPs which made great test cases.
But in all these cases, the protein is still surface-displayed and not actually secreted, so what remained was to show that once the screen had identied a good design, that it was still a good design if it was simply secreted. Thankfully it was!
This was an explosion of data - showing us the best and worst combinations of promoters and signal peptides to use for each target protein to reveal the importance of these modular parts for each case. Very useful data for informing future designs, training AI and maybe uncovering rules.
So armed with the modular toolkit, the YSD-based method and a FACS-based screen-and-sort approach, Stacey was able to engineer yeast cells to secrete classic enzyme targets like beta-lactamase, as well as complex structural proteins such as Elastin Like Polypeptides (ELPs).