We kept being busy!

​It has been another year of hard work, leaving little time for regular updates. Much of our effort culminated in milestones reached during a roller-coaster December that is only now slowing down as the holidays approach. Time to recap, shall we?

A key milestone was the publication of our iPS2-seq paper on Molecular Systems Biology, which marks the completion of the first major project (almost) entirely conceived and developed since establishing the lab in Torino. Elisa, Maria, and Kirsten led different aspects of this interdisciplinary effort: a real behemoth that combines a technological tour de force with some genuinely exciting new biology. In short (you can read the press release for more details), iPS2-seq is our most advanced method yet to perform phenotype-agnostic pooled functional screens in hiPSCs and their differentiated derivatives. It overcomes what, in our humble opinion, have been some of the major technical roadblocks holding the field back. Its most distinctive feature is the ability to follow individual clones both in the absence and presence of an inducible perturbation; something we show to be essential for correct data interpretation, particularly when controlling for epigenetic biases (which, boy, we had underestimated!).

We are very proud of this publication. It builds upon the nearly ten-year-old opti-kd method I developed during my PhD, elevating it to enable multi-omic single-cell readouts. On a more personal note, the first pilot experiments for iPS2-seq, now decorating the Appendix of the manuscript, date back to my late postdoctoral work in Seattle. After a pandemic, an intercontinental move, and a lot of troubleshooting and optimization, it is immensely satisfying to see this idea finally realised and out in the open. We made a concerted effort to make the method broadly accessible, with step-by-step protocols and a robust bioinformatic pipeline (catcheR), which we hope will enable many labs to adopt iPS2-seq and make impactful discoveries of their own.

With the help of the talented illustrator Laura Seclì, we proposed a couple of images for the journal cover. I am pleased to share one that did not make the cut, but that I particularly like, as it truly captures the technical essence of iPS2-seq.

The image portrays a “Clone-Aware Differentiation Orchard,” where barcoded stem-cell clones branch into distinct cardiac lineages and yield characteristic “fruits” representing various cell lineages. Through the iPS2-seq single cell multiomic scanner and catcheR sorting arm, clonal identities and perturbation effects are resolved, revealing SMAD2 as a key regulator of cardiogenesis and uncovering a subset of epigenetically biased clones with aberrant developmental potential.  Image credit: Laura Seclì. License:​ CC-BY NC 4.0

​A closely related milestone is our first grant under the Fondazione Telethon umbrella, in partnership with Fondazione Cariplo (press release). This pilot project aims to demonstrate that iPS2-seq can serve as a reference method to study TDarks—understudied genes that may hold the key to many genetic diseases. We have specifically identified ten such genes implicated in congenital heart defects, which we will investigate using cardiac organoids. We are very pleased to have received this support and look forward to starting the work in 2026.

​Another important funding milestone was securing a Good Food Institute grant to continue our cellular agriculture program (press release). In a turbulent year for the field within the private sector, we feel privileged to receive non-profit funding to develop cell lines that will be publicly distributed at the end of the project, enabling broader advances by other groups. ​This success builds on the foundation laid by last year’s CultMeat crowdfunding campaign and our ongoing proof-of-concept grant from Fondazione Sanpaolo (which, I realize, we may never have officially announced or celebrated—better late than never!). Together, these efforts nicely illustrate how every contribution—however small, as in the case of individual crowdfunding donations—can multiply its value many-fold (about six times in this case, considering the University’s matching) to support slow but steady progress in a field that still requires substantial rigorous science to meet the triad challenges of cost parity, scalability, and exceptional taste and nutrition.

Our manuscript pipeline continues to move forward steadily, in line with our philosophy of early dissemination, transparent peer review, open science, and society journal publishing. This year this included revising our manuscript on home-made media, now accepted in Open Research Europe; publishing a second manuscript in the same venue on preventing silencing of doxycycline-inducible systems (a nemesis of mine since my PhD, which we believe we have finally cracked: more to come in the upcoming revision!); and receiving our first peer reviews through Review Commons for Silvia’s PhD paper.

Milestones, of course, do not stop at papers. Our two patents for GERALT and CIRI, originally filed in June 2024, were just published by WIPO in their upgraded form. We added substantial new data via PCT Direct, strengthening the validation of both methods and, for GERALT, securing a positive assessment on all three key criteria: inventive step, novelty, and industrial applicability. We are excited to engage with prospective licensees while continuing to develop the technologies, both for human model development and for longer-term applications in cultivated meat. Stay tuned for the upcoming manuscripts, which we plan to preprint in early 2026.

Relatedly, the two scientific leads behind the GERALT and CIRI stories are now officially the first PhD graduates of the Bertero lab, having defended their theses at the start of December: congratulations to Sveva and Federica! This was a particularly special moment for yours truly, especially as one of the external examiners was my own PhD advisor, Prof. Ludovic Vallier: a genuine closing of the circle. I must admit I was almost as nervous as the two candidates during the defenses, but they made the lab proud.

Sveva and Federica (left and right), proudly holding their theses alongside Prof. Ludovic Vallier and yours truly.

​Exceptional graduations, however, are not limited to the PhD level. Sara’s bachelor thesis, “On Multi-Omics and Deep Learning Approaches to Interchromosomal Network Analysis,” thoroughly impressed the committee, as did the record nineteen cum laude exams that culminated in her full-marks graduation in biotechnology.

Sara & team, during a warmer time of the year.

Our now four-year-old lab has also evolved significantly this year. Alongside a healthy turnover, in line with typical training lengths for a mature group, we consolidated our senior personnel with Matteo, who joined us as an RTDa in October, and Elisabeth, who earned the Department’s first research fellow contract, also in October. Our “team of teams” philosophy aims to leverage their expertise and ambitions, together with Elisa’s, to maximise impact across our research areas while maintaining technological competitiveness.

There has been much, much more, of course (dissemination, teaching, grant reporting, traveling, ...), but before this turns into a fully fledged novel, I should probably stop here. Thank you, and congratulations, if you made it this far.
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2026 promises to be a very busy year, in the best possible way, and I very much look forward to seeing many of these efforts come to fruition.