Prof. Patrick Pausch from the Life Sciences Centre—European Molecular Biology Laboratory (LSC-EMBL) partnership institute at Vilnius University (VU) has been awarded a prestigious European Research Council (ERC) Starting Grant of €1.5 million for his innovative research project "Jumbo Phages in Translational Enzyme Research" (JUPITER). Over the next five years, Prof. Pausch and his team at VU will explore jumbo phages—a class of large viruses that infect bacteria—by studying their uncharacterized genes and potential applications in biotechnology.

Advancing Biotechnology

Jumbo phages are viruses with genomes up to ten times larger than typical phages. Only recently has the diversity of jumbo phages been recognized, and much of the genetic content remains unexplored, considerably limiting the understanding of their biology and potential applications. The JUPITER project aims to bridge this gap by employing a novel high-throughput strategy to annotate the functions of unknown genes within jumbo phages.

"This grant offers a unique opportunity to push the boundaries of what we know about jumbo phages. I believe it could lead to groundbreaking molecular tools and methods that may be biotechnologically valuable," said Prof. Pausch.
Prof. Pausch's research is expected to provide new insights into how jumbo phages modulate genetic material and hijack the gene expression machinery of their bacterial hosts. By understanding these processes, the project aims to inspire new antimicrobials, particularly against drug-resistant bacteria, and to create innovative genome-editing tools with wide-ranging applications—from treating genetic diseases to improving agricultural crops.

"Phages are remarkably skilled at taking control of bacterial cells," explained Prof. Pausch. "By studying underexplored genes, we hope to discover new mechanisms and functions that could lead to exciting applications in biotechnology."

Expanding Phage Diversity for Future Discoveries

The large genomes of jumbo phages contain many genes of unknown functions, potentially holding the key to major scientific advancements. "Jumbo phages are big viruses that attack bacteria, and understanding their genes at a large scale will help us to understand their biology in greater detail," said Prof. Pausch. He also noted that the term "jumbo" comes from the famous giant elephant named Jumbo, a name now used to describe other large things, such as jumbo jets.

A key goal of the JUPITER project is to expand the known diversity of jumbo phages. This could accelerate scientific discovery by revealing a broader range of biological mechanisms. Prof. Pausch's collaborative work will include leading researchers from Vilnius University, Drs. Eugenijus Šimoliūnas and Darius Kazlauskas, and provide opportunities for both graduate and undergraduate students to participate, contributing to the development of future scientific talent.

"Together with my team, we are planning to explore the environments of Lithuania to discover new phages and their host bacteria. I am particularly excited to sample previously overlooked environmental niches across the country."

Lithuania and Vilnius University: A Growing Hub for Life Sciences

Prof. Pausch's selection marks a significant achievement for Lithuania and VU. The ERC Starting Grant is one of Europe's most prestigious research funding opportunities, awarded to early-career researchers. For the 2024 ERC Starting Grants, 3500 applications were submitted, and only 495 were selected for funding after two selection rounds. These grants are awarded to researchers 2-7 years after the award of their Ph.D. degree.

"Receiving an ERC Starting Grant is a unique opportunity since grants that fund 'high-risk, high-gain' research at such a scale are quite rare. To succeed in an ERC project, everything needs to align perfectly: the principal investigator, the team members and their institution. Securing another ERC grant further demonstrates that Vilnius University, its researchers, and Lithuania are at the forefront of European research." concluded Prof. Pausch.

This year, two Vilnius University scholars became ERC grantees. Apart from Prof. P. Pausch, another Starting Grant was awarded to Prof. Mantas Šimėnas, working in the Faculty of Physics. Before then, Lithuania had only received one other ERC research grant for early-career researchers in 2022 by Prof. Stephen Knox Jones from Vilnius University, LSC-EMBL.

Scientists from Vilnius University's (VU) Life Sciences Centre (LSC) have discovered a unique way for cells to silence specific genes without cutting DNA. This groundbreaking research, led by Prof. Patrick Pausch and published in the journal Nature Communications, reveals a new way how to silence genes that is akin to pressing a "pause" button on certain genetic instructions within cells.

The research team, including doctoral student Rimvydė Čepaitė, Dr. Aistė Skorupskaitė, undergraduate Gintarė Žvejyte and Prof. P. Pausch at Vilnius University, working alongside an international team, uncovered how cells use a specific system to locate and silence unwanted DNA. This system, which could eventually enable safer gene modifications, shows promise for repairing faulty genes that cause diseases.

“Unlike the well-known CRISPR gene-editing system, often described as molecular 'scissors,' the newly studied type IV-A CRISPR system does not cut genes. Instead, it uses an RNA-guided ‘effector’ complex to recruit an enzyme called DinG, which moves along DNA and silences targeted genes in a more subtle manner.” explains Prof. P. Pausch.

According to the researcher, it is fascinating how the system recognizes the precise location on the DNA to begin working: “The system uses two proteins (Cas8 and Cas5) to find a very short sequence motif adjacent to the RNA guide's complementary target DNA. Once both proteins recognize this short sequence, they melt the double-stranded DNA for target sequence interrogation.”

A critical component in this process is the formation of R-loops—open DNA structures where RNA binds, signalling the system to initiate gene silencing.

“The ‘R’ in R-loop stands for RNA. All DNA-binding CRISPR-Cas systems use this structure to probe the DNA sequence and identify the correct target site. Stable R-loops only form in the presence of a DNA sequence that sufficiently matches the guide RNA. The R-loop essentially tells the system when it's appropriate to start silencing a gene,” states the research professor.

In his words, the DinG enzyme further enhances gene suppression by unwinding the DNA strands, allowing the system to exert its effect over a longer DNA sequence.

This discovery opens doors to future applications in genome editing without the risk of DNA cuts, which could lead to more precise tools for research and biotechnology. “Our system’s unique ability to traverse DNA without cutting genes is intriguing for advanced gene-editing applications,” adds Prof. P. Pausch, who believes this new approach could benefit society by enabling safer genetic modifications.

This illustration shows the final model of the type IV-A mechanism. From left to right: Step 1 shows the formation of the "effector" complex, consisting of guide RNA and type IV-A proteins (rendered from a cryo-EM structure). The RNA-protein complex binds to a short motif next to the DNA target site (PAM). In Step 2, an R-loop forms, signalling the target site is found. Step 3 shows the binding of DinG (pink bubblegum-like structure). In Step 4, DinG likely moves along the DNA to silence the gene, potentially repeating the process for further silencing (Step 5).

The European Research Council (ERC) has announced the award of Starting Grants to the most talented early-career researchers. The prestigious funding has been awarded to two representatives of Vilnius University (VU) –Dr Patrick Pausch, a Research Professor from the Life Sciences Center European Molecular Biology Laboratory Partnership Institute (LSC-EMBL, PI), and Dr Mantas Šimėnas, Professor from the Faculty of Physics (FP).

The research group led by Prof. Šimėnas has been awarded EUR 2.5 million over five years for the innovative project ‘Strongly Enhanced Sensitivity EPR through Bimodal Resonators and Quantum-Limited Amplifiers(Strong-ESPRESSO)’.

Šimėnas’s research aims to reduce the time required for EPR experiments by a factor of several thousand and to translate these improvements into the study of new systems. The researcher had previously been awarded a Marie Skłodowska-Curie Postdoctoral Fellowships grant, which allowed him to improve the sensitivity of the EPR tool several hundred times.

The EUR 1.5 million grant will enable the research team led by Prof. Pausch to implement the ground-breaking research pro ject ‘Jumbo Phages in Translational Enzyme Research’ (JUPITER). Over the next five years, the researcher and his team from the LSC-EMBL PI at VU will study jumbo phages – a class of large, bacteria-infecting viruses. The team will analyse their uncharacterised genes and potential applications in biotechnology.

In 2022, Prof. P. Pausch became one of the recipients of the European Molecular Biology Organisation (EMBO) Installation Grant. The ERC Funding will allow him to continue his innovative work.

The total amount of ERC Starting Grants awarded is EUR 780 million. The funding, which a total of 3,500 candidates competed for, is allocated to 494 researchers for five years. To date, the only ERC Starting Grant in Lithuania has been awarded to Dr Stephen Knox Jones, a researcher from the LSC at VU.