Sign in

Filippo Caschera

@stjle.bsky.social
163 followers 231 following 150 posts

Synthetic Biology, Artificial Cells, Amphiphile Systems, Machine Learning, Cell-Free Protein Synthesis: Italy, Denmark, Japan, USA, France, Germany, UK. Cell-Free Protein Synthesis consultant scholar.google.com/citations?user=u…

PostsRepliesMedia
Filippo Caschera @stjle.bsky.social · 29/09/2026
Lights, machines, action! Watching gene expression unfold at the single-molecule level www.sciencedirect.com/science/arti...
011
Filippo Caschera @stjle.bsky.social · 27/09/2026
Artificial Biosynthetic Pathways for Cell-Free Production of Raspberry Ketone and the Cardiotonic Drug Dobutamine pubs.acs.org/asbcd6/artic...
pubs.acs.org
Artificial Biosynthetic Pathways for Cell-Free Production of Raspberry Ketone and the Cardiotonic Drug Dobutamine
Abstract. Raspberry ketone (RK) is a high-value flavor and fragrance compound widely used in the food, beverage, and cosmetic industries. However, existing
000
Filippo Caschera @stjle.bsky.social · 22/09/2026
elifesciences.org/articles/111...
elifesciences.org
A membrane insertion code for intrinsically disordered proteins
A sequence-based method dubbed AroMIP predicts the membrane insertion propensities of aromatic-centered motifs, thereby advancing mechanistic understanding of membrane insertion and enriching the tool...
000
Filippo Caschera @stjle.bsky.social · 21/09/2026
www.nature.com/articles/s41...
nature.com
Dosing and delivery of bacteriophage therapy in a murine wound infection model - Nature Communications
Here, the authors develop a mouse model of wound infection to evaluate the efficacy of phage therapy for established infections and generate “HydroPhage”, a phage-containing hydrogel, as a means for s...
000
Filippo Caschera @stjle.bsky.social · 20/09/2026
www.biorxiv.org/content/10.6...
biorxiv.org
Protein expression is amplified by stabilizing mRNA using gene-specific antisense oligonucleotides
Effective and safe strategies to restore gene expression in haploinsufficiency disorders or to augment protective protein signaling have long been attractive but challenging therapeutic goals. Here, w...
010
Reposted by Filippo Caschera
Nature Reviews Bioengineering @natrevbioeng.nature.com · 17/09/2026
Building sustainable diagnostic ecosystems for global health
dlvr.it
Building sustainable diagnostic ecosystems for global health
Nature Reviews Bioengineering, Published online: 17 September 2026; doi:10.1038/s44222-026-00498-4Global access to diagnostics is constrained not only by the availability of testing technologies but also by their dependence on costly supply chains that typically originate from a small number of capital-intensive biotechnology hubs. Here, we argue that integrating decentralized diagnostics with local manufacturing and research capacity is essential to building resilient, equitable and sustainable diagnostic ecosystems.
011
Reposted by Filippo Caschera
Nature Reviews Bioengineering @natrevbioeng.nature.com · 15/09/2026
Biomolecular condensates in cancer therapy
dlvr.it
Biomolecular condensates in cancer therapy
Nature Reviews Bioengineering, Published online: 14 September 2026; doi:10.1038/s44222-026-00493-9Liquid–liquid phase separation (LLPS) is emerging as a key mechanism in cancer, linking biomolecular condensates to oncogenic signalling and tumorigenesis. This Review discusses evidence for dysregulated LLPS and highlights bioengineering strategies that enable therapeutic targeting of previously undruggable cancer drivers.
043
Filippo Caschera @stjle.bsky.social · 08/09/2026
Optimizing multi-gene co-expression with large plasmids www.nature.com/articles/s41...
000
Filippo Caschera @stjle.bsky.social · 01/09/2026
www.science.org/doi/10.1126/...
science.org
Programmable protein degraders enable selective knockdown of pathogenic β-catenin subpopulations in vitro and in vivo
Aberrant activation of Wnt signaling results in unregulated accumulation of cytosolic β-catenin, which subsequently enters the nucleus and promotes transcription of genes that contribute to cellular p...
000
Filippo Caschera @stjle.bsky.social · 31/08/2026
www.tandfonline.com/doi/full/10....
tandfonline.com
Quantifying molecular specificity in excipient-driven antibody solubilization
Excipients are widely used to suppress the self-association of therapeutic proteins, yet their mechanisms of action are not well understood and often assumed to be nonspecific. Here we show that ex...
000
Filippo Caschera @stjle.bsky.social · 27/08/2026
Guidelines for preparing, assessing, and implementing immobilized enzymes for biocatalysis: tackling academic, industrial, and environmental aspects pubs.rsc.org/gc/article/d...
000
Filippo Caschera @stjle.bsky.social · 27/08/2026
www.nature.com/articles/s41...
nature.com
Phage therapy: from basic biology to clinical application - Nature Reviews Microbiology
In this Review, Iredell and colleagues examine key aspects of phage biology and their relevance to phage therapy, and outline current approaches for clinical application of phages, along with their as...
000
Filippo Caschera @stjle.bsky.social · 27/08/2026
www.nature.com/articles/s41...
nature.com
A smartphone-powered decentralized microfluidic platform for sensitive CRISPR-based nucleic acid detection - Microsystems & Nanoengineering
Microsystems & Nanoengineering - A smartphone-powered decentralized microfluidic platform for sensitive CRISPR-based nucleic acid detection
010
Reposted by Filippo Caschera
bioRxiv Synthetic Biology @biorxiv-synthbio.bsky.social · 26/08/2026
ORB-TXTL: cell-free expression of membrane proteins on lipid bilayer-coated beads www.biorxiv.org/content/10.64898/20…
011
Reposted by Filippo Caschera
Nature Methods @natmethods.nature.com · 24/08/2026
ProteinDPO: a protein language model for stability prediction and generation of thermostable protein sequences. @brianhie.bsky.social www.nature.com/articles/s41...
nature.com
Aligning protein-generative models to experimental fitness with ProteinDPO - Nature Methods
This Article demonstrates that direct preference optimization (DPO) can be used to effectively align an unsupervised structure-conditioned language model with biophysical information. The aligned mode...
1103
Filippo Caschera @stjle.bsky.social · 21/08/2026
Accelerating protein design by scaling experimental characterization
nature.com
000
Reposted by Filippo Caschera
Philip Romero @philromero.bsky.social · 18/08/2026
What if AI could interact directly with biology? Congrats to Coban, who gave AI the ability to experiment and learn through feedback. Over 25 autonomous rounds, it uncovered the determinants of enzyme specificity. Give AI the ability to experiment, then get out of the way. doi.org/10.64898/202...
doi.org
Learning protein function through autonomous experimental interaction
Biological AI learns primarily from existing observations, but many questions cannot be answered from available data alone. Here we show that AI can instead acquire knowledge by acting directly on biological systems and learning from the consequences. We developed a closed-loop framework in which autonomous agents design protein variants, construct and characterize them in a robotic laboratory, learn from the resulting experimental feedback, and decide what experiments to perform next. We then allowed the system to operate continuously and without human intervention for approximately one month, during which multiple agents independently explored protein sequence space while learning from shared experimental experience. Applied to glycoside hydrolases, the agents discovered enzymes with substantially altered substrate specificity toward non-native sugars and progressively learned the structure of the underlying sequence-function landscape. The resulting experimental experience also revealed determinants of substrate specificity and protein expression that were not specified as learning objectives. These results demonstrate that AI can autonomously interact with biology over extended periods to acquire knowledge through experience, establishing a framework for biological discovery driven by continuous experimental interaction. ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, 5R01GM150929
1144
Reposted by Filippo Caschera
Nature Biotechnology @natbiotech.nature.com · 19/08/2026
High-throughput synthesis of DNA fragments by molecular self-assembly of overlapping oligonucleotides - @tsinghuauniversity.bsky.social www.nature.com/articles/s41...
nature.com
High-throughput synthesis of DNA fragments by molecular self-assembly of overlapping oligonucleotides - Nature Biotechnology
DNA libraries are synthesized at scale.
1197
Reposted by Filippo Caschera
Nature Biotechnology @natbiotech.nature.com · 17/08/2026
Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells - @juliacarnevale.bsky.social @marsonlab.bsky.social www.nature.com/articles/s41...
nature.com
Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells - Nature Biotechnology
Primary human myeloid cells are efficiently edited using virus-like particles.
1163
Filippo Caschera @stjle.bsky.social · 16/08/2026
onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com
De Novo Discovery of Nonstandard Thioisoindole‐Bridged Bicyclic Peptides Targeting Traf2‐ and NCK‐Interacting Kinase
An optimized strategy for the ribosomal synthesis of thioisoindole-bridged bicyclic (TiB) peptides is incorporated into the RaPID platform, enabling high-throughput discovery from topologically defin....
010
Filippo Caschera @stjle.bsky.social · 16/08/2026
www.nature.com/articles/s41...
nature.com
Massive barcode-free chemical screenings enable the discovery of bioactive macrocycles with passive membrane permeability - Nature Communications
Synthetic macrocycles are promising therapeutics; however, most high-throughput discovery platforms rely on genetically encoded libraries of large peptide macrocycles, which are typically not optimize...
031
Filippo Caschera @stjle.bsky.social · 13/08/2026
www.nature.com/articles/s41...
nature.com
A programmable DNA origami nanosyringe for directed membrane translocation - Nature Nanotechnology
A membrane-anchoring nanodevice that integrates reversible, fuel-driven mechanical actuation enables programmable membrane penetration, cargo delivery and spatiotemporal regulation of biochemical reac...
000
Reposted by Filippo Caschera
Olivier Borkowski @oborkowski.bsky.social · 11/08/2026
Regulation of Escherichia coli fermentation processes: from molecular mechanisms to smart industrial practice doi.org/10.1007/s002...
031
Filippo Caschera @stjle.bsky.social · 09/08/2026
onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com
Conformation‐Guided Disulfide Pairing Enables Efficient Folding of Disulfide‐Rich Peptides
Extensive conformational sampling identifies a folding-promoting disulfide bond that controls the oxidative folding pathway of disulfide-rich peptides. Exploiting this principle enables a generalizab....
010
Filippo Caschera @stjle.bsky.social · 30/07/2026
www.biorxiv.org/content/10.6...
biorxiv.org
Crowdsourced riboregulators reveal design principles for programmable RNA switching
RNA-based sensors offer powerful and programmable control of gene expression, yet our understanding of the structural principles that govern their potential design space remains incomplete. Here, we c...
000
Reposted by Filippo Caschera
Cees Dekker @ceesdekker.bsky.social · 22/07/2026
We built a a self-dividing synthetic cell ! Check out this #CDlab preprint on BioRxiv: www.biorxiv.org/content/10.6... Great work by 1st author Charu Sharma who encoded dynaminA in a genome and expressed that in liposomes that then divide into daughter cells! Collaboration with Koenderink lab!
24726
Filippo Caschera @stjle.bsky.social · 18/07/2026
pubs.acs.org/doi/10.1021/...
pubs.acs.org
Machine Learning Models for Local Optimization of Red Fluorescent Protein Variants in a Low-Data Setting
Fluorescent proteins (FPs) are widely used reporters for visualizing cellular structures and processes. Traditional wet-lab strategies for FP engineering (rational design and directed evolution) have ...
011
Filippo Caschera @stjle.bsky.social · 18/07/2026
www.cell.com/molecular-ce...
cell.com
Granular component sub-phases direct ribosome biogenesis in the nucleolus
Dogra et al. use super-resolution microscopy to uncover the molecular origins of spatial heterogeneity in the nucleolar granular component (GC). They show that differential interactions of nucleolar p...
010
Filippo Caschera @stjle.bsky.social · 17/07/2026
www.nature.com/articles/s41...
nature.com
De novo design of peptides localizing at the interface of biomolecular condensates - Nature Communications
Combining high-throughput molecular simulations, machine learning, and mixed-integer linear programming, the authors design peptides that localize to condensate interfaces, revealing surfactant-like, ...
010
Reposted by Filippo Caschera
Cees Dekker @ceesdekker.bsky.social · 13/07/2026
Latest #CDlab paper: a review entitled 'Devising a divisome for synthetic cells' in Nature Reviews Chemistry www.nature.com/articles/s41... Here, 1st authors Joris Dommisse and Rafael Lira review current strategies to mimic division: symmetry breaking, constriction and abscission. Enjoy the read!
033
Reposted by Filippo Caschera
Shuai Wang @wshuai.bsky.social · 10/07/2026
So proud to see this study out — a real honor to be involved in work from my PhD lab!
0114
Reposted by Filippo Caschera
bioRxiv Synthetic Biology @biorxiv-synthbio.bsky.social · 10/07/2026
Transcription-induced coacervation accelerates and sensitizes cell-free biosensing www.biorxiv.org/content/10.64898/20…
001
Filippo Caschera @stjle.bsky.social · 07/07/2026
Improving cell-free metabolism through direct integration of artificial respiratory chains www.pnas.org/doi/10.1073/...
000
Reposted by Filippo Caschera
Chris Ashwood @cashwood.proteaglyco.com · 03/07/2026
MS only measures m/z, but what if we could tell it what molecules those m/z values are during the run? Our preprint introduces GlycoRTMS: real-time, glycan-aware acquisition that annotates precursors with glycans and uses that context to steer fragmentation #glycotime www.biorxiv.org/content/10.6...
biorxiv.org
Contextualised real-time mass spectrometry improves glycosylation detection and characterisation
Glycosylation is a structurally diverse, non-template-driven modification whose analysis by liquid chromatography-mass spectrometry is constrained by discovery-mode acquisition rules developed for pro...
2258
Filippo Caschera @stjle.bsky.social · 03/07/2026
www.science.org/doi/10.1126/...
science.org
Membrane protein solubilization and structure determination using de novo–designed proteins
Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a gener...
000
Filippo Caschera @stjle.bsky.social · 29/06/2026
www.nature.com/articles/s41...
nature.com
Engineered circular RNA compatible with complete nucleoside modification and rolling circle translation through a Cap-independent translation enhancer - Nature Biomedical Engineering
A suite of tools to improve translation and immunogenicity of circular RNAs, including nucleoside modification and rolling circle translation, for applications in cancer vaccines, protein replacement ...
000
Reposted by Filippo Caschera
Olivier Borkowski @oborkowski.bsky.social · 29/06/2026
Our paper "Active-learning-guided optimization of cell-free systems for genome-wide transcriptomic profiling reveals progressive layers of regulation" is online in Nature Communications! Congrats Lea Wagner, very proud of this work! www.nature.com/articles/s41... #cellfree #AI #T7Phage #synbio
nature.com
Active-learning-guided optimization of cell-free systems for genome-wide transcriptomic profiling reveals progressive layers of regulation - Nature Communications
Cell-free is a powerful platform to unravel biological complexity. Here, the authors used active learning to optimize buffer composition, boosting mRNA 20-fold, enabling cell-free transcriptomics and ...
1139
Filippo Caschera @stjle.bsky.social · 25/06/2026
www.nature.com/articles/s44...
nature.com
Decentralized molecular diagnostics for viral diseases - Nature Reviews Bioengineering
Viral diseases continue to impose a major global health burden, yet substantial inequities in access to accurate molecular diagnostics persist, limiting effective surveillance and response. This Revie...
000
Filippo Caschera @stjle.bsky.social · 23/06/2026
pubs.acs.org/doi/10.1021/...
pubs.acs.org
Development of a High-Throughput Size-Exclusion Chromatography–Mass Spectrometry Workflow for Real-Time Monitoring of Bioconjugation of Cysteine-Based Antibody–Drug Conjugates
The manufacturing of cysteine-based antibody–drug conjugates (ADCs) requires precise control of the drug-to-antibody ratio (DAR), a critical quality attribute influencing product safety and efficacy. Conventional analytical techniques used for DAR determination, such as hydrophobic interaction chromatography (HIC) and reversed-phase high-performance liquid chromatography (RP-HPLC), are low-throughput and unsuitable for real-time process monitoring, limiting process development efficiency. To address this challenge, we developed a high-throughput size-exclusion chromatography–mass spectrometry (SEC-MS) workflow with and without postcolumn denaturation (PCD) functionality, enabling real-time monitoring of both reduction and conjugation kinetics during cysteine-based ADC manufacturing. Using a short SEC column coupled to a mass spectrometer, analysis time can be performed under 2 min per sample. This workflow was applied to rapidly optimize critical process parameters, including reductant concentration and pH during reduction, and drug-linker ratio during conjugation. The approach provided deeper mechanistic insights into reaction kinetics and supports process analytical technology (PAT)-enabled strategies for advanced process control. Overall, this high-throughput SEC-MS workflow accelerates ADC development while improving manufacturing robustness.
000
Filippo Caschera @stjle.bsky.social · 21/06/2026
www.nature.com/articles/s41...
nature.com
The biology of jumbo phages - Nature Communications
Jumbo phages are bacterial viruses with double-stranded DNA genomes exceeding 200 kb. In this Review, Sam van Beljouw & Li Yuping examine the biology of these bacteriophages, highlighting their di...
000
Filippo Caschera @stjle.bsky.social · 19/06/2026
High-throughput functional profiling and evolutionary covariation analysis of entire riboswitch sequences academic.oup.com/nar/article/...
academic.oup.com
High-throughput functional profiling and evolutionary covariation analysis of entire riboswitch sequences
Abstract. Riboswitches are useful models for revealing how some RNA molecules undergo dynamic rearrangements of their structures to perform cellular functi
010
Filippo Caschera @stjle.bsky.social · 17/06/2026
www.biorxiv.org/content/10.6...
biorxiv.org
Structural modularity of receptor-binding proteins underlies host-range strategy diversification in Klebsiella pneumoniae phages
Bacteriophage receptor-binding proteins (RBPs) determine bacterial host recognition and are central to phage host-range evolution, yet the structural principles governing how RBPs diversify and expand...
000
Reposted by Filippo Caschera
Olivier Borkowski @oborkowski.bsky.social · 17/06/2026
Rapid Affinity Characterization of Cell-Free Expressed Nanobodies Directly in Lysate with Biolayer Interferometry via Antigen-Immobilized Biosensors pubs.acs.org/doi/10.1021/...
pubs.acs.org
Rapid Affinity Characterization of Cell-Free Expressed Nanobodies Directly in Lysate with Biolayer Interferometry via Antigen-Immobilized Biosensors
There have been a few recent works showing the advantages of combining cell-free protein expression (CFE) with biolayer interferometry (BLI) for the rapid kinetic characterization of novel capture pro...
001
Filippo Caschera @stjle.bsky.social · 13/06/2026
Discovery and engineering of polymerases and ligases for the synthesis of modified nucleic acids www.sciencedirect.com/science/arti...
000
Reposted by Filippo Caschera
Kerstin Göpfrich @kgoepfrich.bsky.social · 10/06/2026
Happy to share our latest work in collaboration with IBEC. Congratulations to recent PhD graduate and lead author @towalther.bsky.social!
011
Reposted by Filippo Caschera
cryoEM papers @cryoempapers.bsky.social · 10/06/2026
Accurate de novo design of peptides from programming biophysical landscape www.biorxiv.org/content/10.64898/2026.06.08.731011v1 #cryoEM
122
Filippo Caschera @stjle.bsky.social · 05/06/2026
arxiv.org/abs/2606.05474
arxiv.org
AlloGen: Conformation-Selective Binder Generation with Differential State Scoring
Protein binder design has largely optimized for affinity alone, leaving conformational selectivity unaddressed: for allosteric targets such as kinases, nuclear receptors, and GPCRs, a binder that enga...
000
Filippo Caschera @stjle.bsky.social · 01/06/2026
arxiv.org/abs/2605.31296
arxiv.org
mRNAutilus: Multi-Objective-Guided Discrete Generation of mRNA with Optimized Therapeutic Properties
Therapeutic mRNA design requires coordinating multiple interacting sequence features across the full transcript, where codon usage, untranslated regions (UTRs), and their coupling jointly determine st...
000
Filippo Caschera @stjle.bsky.social · 30/05/2026
www.sciencedirect.com/science/arti...
sciencedirect.com
Stabilization strategies and advancements in lyophilization to preserve integrity and efficacy of next-generation biologicals
The success of mRNA-lipid nanoparticles (LNPs) vaccines during the COVID-19 pandemic has significantly increased global demand for stable, thermo-resi…
000