Tom Ellis
@proftomellis.bsky.social
3.1K followers 350 following 290 posts
Synthetic Biology & Synthetic Genomics @ Imperial College London and the Sanger Institute. Bilingual in English and DNA. Views are either my own or my microbes'
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proftomellis.bsky.social
Another new paper from our lab - this time from Anastasiya Kishkevich who has developed "YTK Display-and-Secrete" a library-based method to identifying genetic designs good for protein secretion from S.cerevisiae yeast. Online now at ACS SynBio - pubs.acs.org/doi/10.1021/...
proftomellis.bsky.social
Loved the bit about ‘See It Say It Sorted.’ My 4 year old is convinced it is “See It Say It Sausage” and even shouts that on the train when the announcement is made. I can never unhear it.
Reposted by Tom Ellis
proftomellis.bsky.social
Yesterday was the first day of autumn and guess what appeared in the window of the Peninsula hotel in London.
proftomellis.bsky.social
astly I also want to shout-out to Morgane Boone and Nico Callewaert whose SECRiFY project at VIB Ghent gave us lots of the inspiration for this work. www.nature.com/articles/s41...
proftomellis.bsky.social
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.
proftomellis.bsky.social
There's more to this paper too but I'll leave it here as this is the key to the work. Modular libraries, FACS-based YSD-enabled screening and POLAR-seq will fast-track finding an optimal design. And then this gene cassette design can be kept as the design used for good secretion.
proftomellis.bsky.social
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!
proftomellis.bsky.social
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.
proftomellis.bsky.social
Stacey and Klaudia applied POLAR-Seq to the libraries of yeasts we were making with different cassette designs for secretion of target proteins. The FACS-based screen sorted the libraries of yeasts into good, medium and bad secretors and POLAR-seq then determined all genotypes.
proftomellis.bsky.social
But here's where it gets a bit cooler - we recently developed POLAR-Seq in our lab which can be used to directly sequence all the different genetic designs found in a targeted region of the yeast genome in a pool of cells from a combinatorial library. www.biorxiv.org/content/10.1...
Combinatorial Design Testing in Genomes with POLAR-seq
Synthetic biology projects increasingly use modular DNA assembly or synthetic in vivo recombination to generate diverse combinatorial libraries of genetic constructs for testing. But as these designs ...
www.biorxiv.org
proftomellis.bsky.social
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).
proftomellis.bsky.social
As others have shown before, this YSD-based approach means you can label cells with epitope-binding fluorescent antibodies and then use flow cytometry to sort the ones with the most of your target protein attached to them. These should be the best secretors.
proftomellis.bsky.social
But this required a screening method that could test 1000s of cells for secretion of a target protein. For this she adapted Yeast Surface Display (YSD) to attach epitope-tagged proteins to the outside of the cells that secreted them. This was done in modular format to fit YTK.
proftomellis.bsky.social
We and many others use the YTK MoClo system to assemble genes from parts in yeast and it's ideal for generation of combinatorial libraries. Stacey reasoned that this could be adapted to make libraries of gene cassette designs that can be screened for secretion of a given protein.
proftomellis.bsky.social
This paper is all about taking a combinatorial approach to the age-old biotech problem of how to design a gene cassette to secrete a protein of interest from yeast. What strength promoter to use? Which signal peptide? The best choice varies widely depending on the protein target.
proftomellis.bsky.social
Another new paper from our lab - this time from Anastasiya Kishkevich who has developed "YTK Display-and-Secrete" a library-based method to identifying genetic designs good for protein secretion from S.cerevisiae yeast. Online now at ACS SynBio - pubs.acs.org/doi/10.1021/...
Reposted by Tom Ellis
biorxiv-synthbio.bsky.social
Genetic entanglement enables ultra-stable biocontainment in the mammalian gut https://www.biorxiv.org/content/10.1101/2025.08.13.670093v1
proftomellis.bsky.social
🚨 What do you mean?
🇩🇯 Normal people always
👏 write like this
Reposted by Tom Ellis
sudpinglay.bsky.social
We are hiring a scientist to lead our 'Build' team at the Seattle Hub for Synthetic Biology. @alleninstitute.org

Job posting below:
alleninstitute.org/careers/jobs...

Please reach out if you have any questions!
Jobs
We are working to solve the biggest mysteries in bioscience.
alleninstitute.org
proftomellis.bsky.social
This paper was led by Jane during her PhD and included some of Glen's unpublished PhD work as well as key contributions from Klaudia Ciurkot (POLAR-Seq) and Will Shaw (CRISPR) @willshaw.bsky.social
- Always a pleasure to have amazing people like this in my group and talk about their work.
proftomellis.bsky.social
These datasets and others like it from our lab are now being used to help us train AI models for synthetic yeast genome design that can consider gene context and arrangement effects - features hard to assess using natural genomes. Keep an eye on @biorxiv-synthbio.bsky.social for more soon.
proftomellis.bsky.social
ogether, Jane and Glen's work provide important insights into the effectiveness of gene rearrangement in synthetic genomes for improving fitness and identifying design changes for optimisation. They also offer unique data on how altering gene context changes gene expression.