Yuping Li Wins €1.5M ERC Grant to Decode How Bacteria Fight Jumbophages

One of the most unusual arms races in microbiology is about to receive major European funding.

Yuping Li, microbiologist and tenure-track Assistant Professor at the Biozentrum of the University of Basel, has been awarded a European Research Council Starting Grant worth €1.5 million over five years to investigate how bacteria detect and stop jumbophages — exceptionally large bacteriophages whose infection strategies can allow them to evade some of the best-known bacterial immune systems.

Yuping Li - Biozentrum Basel

The ERC-funded project is titled “Special phages call for special defences: mechanisms underlying immune sensing of nucleus-forming jumbophages.” Its central question is deceptively simple: if these giant phages physically shield their genetic material from bacterial immunity, how do bacteria nevertheless recognize that an infection is taking place?

Answering that question could reveal previously unknown principles of bacterial immunity, expose key proteins used by jumbophages during infection and ultimately improve understanding of how unusually large phages might be exploited against antibiotic-resistant bacteria.

The award also comes during an exceptionally competitive ERC Starting Grant round. In 2026, the European Research Council received a record 4,807 proposals and selected 421 researchers, corresponding to a funding rate of only 8.8%. The ERC committed €705 million to the round, with Starting Grants generally providing up to €1.5 million over five years. Thirty-six of the successful projects will be hosted in Switzerland.

Li is one of six women at the University of Basel to receive an ERC Starting Grant in the 2026 competition. The successful Basel projects span jumbophage biology, cancer immunology, neuroscience, architectural history, Soviet minority policy and microbiome development.

For phage biology, however, Li's project addresses a particularly fundamental problem.

Jumbo bacteriophages are generally defined as double-stranded DNA phages with genomes larger than 200 kilobases. Their genomes can encode hundreds of genes, many with functions that remain unknown, and some members have evolved infection mechanisms with a level of spatial organization rarely associated with viruses of bacteria. A 2026 review by Sam van Beljouw and Yuping Li described them as an extraordinarily diverse class of bacterial viruses whose large genomes provide extensive genetic space for unusual molecular machinery.

Among the best studied are ϕKZ-like jumbophages that infect Pseudomonas aeruginosa.

Their infection strategy presents bacteria with an unusual defensive problem. Soon after entering the bacterial cell, ϕKZ-like phages can establish a lipid-associated early phage infection compartment, or EPI vesicle. Later, they assemble a proteinaceous nucleus-like structure around their genome.

This “phage nucleus” is not a true eukaryotic nucleus, but functionally the analogy is striking. Viral DNA replication and parts of the transcriptional programme occur inside a dedicated protein shell that physically separates the genome from much of the bacterial cytoplasm.

That separation can protect the viral DNA from host defence systems that depend on directly accessing genetic material.

Previous work has shown that DNA-targeting CRISPR systems and restriction enzymes can be ineffective against nucleus-forming jumbo-phages because their nuclease machinery cannot easily reach the protected phage genome. RNA-targeting immune mechanisms can circumvent this barrier because viral messenger RNAs must eventually become accessible outside the compartment for translation, but these systems are comparatively uncommon.

From the bacterium's perspective, this creates a serious problem. Many antiviral systems detect foreign nucleic acids. But what happens when the invading virus hides its nucleic acid almost immediately?

Li's previous research provided one of the most important answers to that question.

During her postdoctoral work in Joseph Bondy-Denomy's laboratory at the University of California, San Francisco, Li led the discovery of a bacterial immune system specifically adapted to nucleus-forming jumbo-phages. The researchers named it Juk, for “jumbo phage killer.”

The study, published in Cell in 2025, showed that Juk does not need to wait until it can attack the protected viral genome. Instead, it detects an early stage of the infection itself.

The system consists of a sensor called JukA and an associated effector, JukB.

During ϕKZ infection, an early phage protein called gp241 is produced in association with the early infection compartment. JukA can bind this phage protein and subsequently recruit JukB. The JukB protein forms oligomeric structures with characteristics of a pore-forming effector and disrupts the normal functioning of the early phage infection vesicle.

The consequences for the virus are severe. Early viral gene expression is suppressed, phage DNA replication does not proceed normally and formation of the later phage nucleus is prevented. In this case, the bacterial cell can survive rather than simply sacrificing itself through an abortive-infection mechanism.

That discovery fundamentally changed the way the interaction can be viewed.

Rather than trying to penetrate the jumbophage's defensive shell, bacteria can recognize components required to build or operate that shell before the infection reaches the protected stage.

Li and colleagues also found that the principle extends beyond a single defence pair. JukA-like sensors occur across multiple bacterial phyla and can be associated with different effector proteins, suggesting that evolution has repeatedly coupled recognition of this distinctive phage biology to diverse antimicrobial responses.

There are additional layers of complexity.

Deleting gp241 from ϕKZ did not completely allow the phage to escape every Juk system. In the 2025 experiments, the mutant remained susceptible to one Juk system, suggesting that bacteria may recognize additional or partly redundant signals associated with jumbo-phage infection. Other Juk variants responded differently. The finding hints at a much broader recognition network than a simple one-sensor/one-viral-protein interaction.

The new ERC project appears designed to push directly into this unexplored territory.

According to the Biozentrum, Li's team wants to determine precisely how bacterial sensors recognize phage-specific proteins and, crucially, what those viral proteins actually do during infection.

This second part is particularly interesting because most genes in jumbophage genomes remain poorly characterized.

Bacterial immunity could therefore become more than something to study in its own right. It could become an experimental tool for discovering phage biology.

If evolution has repeatedly selected a bacterial immune sensor that recognizes a particular phage protein, that recognition may indicate that the viral protein performs an important and difficult-to-replace function. Studying what the bacterium “chooses” to monitor can therefore direct researchers toward critical molecular steps in the viral life cycle.

Li explicitly describes this as one goal of the new research: establishing the concept of using bacterial immune systems as tools for identifying and understanding proteins important during phage infection.

Her laboratory at the Biozentrum is already structured around this broader question of bacteria-jumbophage co-evolution.

The group uses genetics, microscopy, biochemistry and structural biology to determine how Juk systems stop ϕKZ-like phages and how the viruses in turn evolve mechanisms that overcome bacterial immunity. High-throughput sequencing and mathematical modelling are also being used to investigate the evolutionary dynamics of these interactions in experimental and natural systems.

This combination of approaches reflects Li's scientific background.

She initially trained in bioinformatics, receiving a Bachelor of Engineering from Huazhong University of Science and Technology in Wuhan. She then moved to Stanford University for her PhD, where she worked with Gavin Sherlock and Dmitri Petrov between 2013 and 2019 on microbial evolution, adaptation and fitness trade-offs. One of her studies examined how apparently simple selective environments can generate unexpectedly complex adaptive outcomes in experimental yeast populations.

After Stanford, Li joined Joseph Bondy-Denomy's group at UCSF, moving from microbial evolutionary genetics toward bacterial antiviral immunity and jumbophage biology. She also spent time as a visiting scientist with Athanasios Typas at EMBL Heidelberg between 2022 and 2023 before establishing her independent group at the Biozentrum in 2024.

The Juk work was itself highly collaborative. The Cell study involved researchers from UCSF, Beijing University of Chemical Technology, EMBL, the US National Institutes of Health and the Chan Zuckerberg Institute for Advanced Biological Imaging, bringing together bacterial genetics, proteomics, bioinformatics, structural biology and advanced imaging.

Li's laboratory has since continued expanding this research programme in Basel.

In June 2026, Li and postdoctoral researcher Sam van Beljouw published an extensive Nature Communications review, “The biology of jumbo phages,” synthesizing current understanding of the genetics, cellular organization, evolution and potential applications of these unusually large viruses. The work was supported in part by Li's earlier Swiss National Science Foundation Starting Grant.

That SNSF award is another important part of the story.

Li received an SNSF Starting Grant announced in late 2024, worth approximately one million Swiss francs over five years, for a project called “Fundamental phage-host biology towards next-generation phage therapy.” The Swiss programme had served as a transitional funding mechanism during the period when Switzerland's participation in Horizon Europe limited access to ERC competitions.

The new €1.5 million ERC award therefore reinforces a research direction that Li has been building since her postdoctoral work: using the exceptional biology of jumbo-phages to uncover fundamental principles of virus-host interaction while asking whether those principles can eventually be exploited therapeutically.

That final possibility is particularly relevant to Pseudomonas aeruginosa.

P. aeruginosa is an opportunistic pathogen capable of causing difficult-to-treat infections and is a major target of contemporary phage-therapy research. Jumbophages can be attractive in this context because some infect broad collections of isolates within a bacterial species and encode sophisticated machinery for overcoming bacterial barriers. Li's group notes that the broad infectivity observed for some jumbo-phages makes them potentially useful against drug-resistant bacteria.

There is already experimental evidence that jumbo-phages can kill clinically relevant resistant P. aeruginosa isolates. The recent jumbo-phage literature reviewed by Li and van Beljouw includes reports of jumbo-phages active against extensively drug-resistant P. aeruginosa associated with contaminated eyedrop infections.

But large genomes and elaborate infection mechanisms do not automatically make a phage therapeutically superior.

The same evolutionary sophistication that allows jumbo-phages to evade CRISPR or restriction systems has driven bacteria to evolve highly specialized countermeasures such as Juk. Understanding those countermeasures may therefore become essential when selecting or engineering therapeutic phages.

A candidate phage can possess an apparently broad receptor-based host range and still fail after genome injection if the target bacterium carries an intracellular defence system capable of detecting and stopping it.

Conversely, learning exactly which viral proteins activate Juk-like immunity could reveal routes by which jumbophages naturally evade those systems. That information might eventually contribute to rational phage selection, the prediction of effective phage-host combinations or engineering approaches designed to avoid specific bacterial immune barriers.

Those applications remain future possibilities rather than demonstrated outcomes of the ERC project.

The new grant is fundamentally aimed at basic research. It will not itself establish jumbophage therapy as a clinical treatment for antibiotic-resistant infections, and understanding an immune sensor does not automatically produce a therapeutically optimized phage.

Its importance lies earlier in the translational chain.

Modern phage therapy increasingly depends on understanding why a phage succeeds or fails inside a particular bacterial strain. Adsorption and receptor recognition represent only the first barriers. Once viral DNA enters the cell, restriction-modification systems, CRISPR-Cas, abortive-infection systems and dozens of more recently discovered defence families can determine whether productive infection occurs.

Jumbophages add another layer to this arms race by physically compartmentalizing their infection.

The discovery of Juk showed that bacteria have responded by evolving an equally unusual strategy: rather than simply attacking exposed viral DNA, they can detect proteins associated with the very structures that hide it.

The ERC project now asks how far that principle extends.

If Li's group can identify the molecular logic through which bacteria sense nucleus-forming jumbophages, the work may uncover new bacterial immune mechanisms, new essential viral proteins and new vulnerabilities on both sides of the phage-host interaction.

And for phage therapy, that could eventually help answer one of the field's most important questions: not simply whether a phage can infect a bacterium in a standard laboratory assay, but whether it can survive the full immune landscape encountered after entering the cell.

Sources : 

Biozentrum, University of Basel — “ERC Starting Grant for Yuping Li,” 3 September 2026. The official announcement confirms the €1.5 million, five-year award and the project's focus on bacterial detection of jumbophages.
Biozentrum announcement

European Research Council — “ERC Starting Grants: €705 million to back Europe's next generation of researchers,” 3 September 2026.
ERC Starting Grants 2026 results

University of Basel — “Six researchers receive an ERC Starting Grant,” 3 September 2026.
University of Basel announcement

Li Y. et al. — “Jumbo phage killer immune system targets early infection of nucleus-forming phages,” Cell 188, 2127–2140.e21 (2025), DOI 10.1016/j.cell.2025.02.016.
Cell study

van Beljouw S.P.B. & Li Y. — “The biology of jumbo phages,” Nature Communications 17, 5458 (2026), DOI 10.1038/s41467-026-74333-0.
Nature Communications review

Biozentrum — Yuping Li Research Group, describing ongoing work on ϕKZ, Juk immunity, evolution and the potential of jumbophages against drug-resistant bacteria.
Yuping Li Research Group