Catalonia plays in the European research Champions League

It is called Mycoplasma pneumoniae and, despite being very simple, this small bacterium with only 680 genes could play a key role in fighting lung cancer, the type of tumor that causes the most deaths each year worldwide: nearly two million. I'researcher Luis Serrano and its team, at the Centre for Genomic Regulation in Barcelona (CRG), have spent years studying this microorganism and genetically modifying it to strip it of its ability to cause disease. Now they want to turn it into a kind of Trojan horse capable of releasing drugs against tumor cells only in the lung.

The objective, Serrano explains to ARA, is to try to "reduce the toxic effect that many drugs and biological treatments have when administered systemically".

The biologist and his team will turn the bacterium into a living pill: they will load it with a deactivated version of the drug and only when M. pneumoniae arrives in the lung will release this therapeutic molecule which, following a perfect choreography, will be activated to have exclusively a local effect.

"We will use protein design and generative artificial intelligence to create the biological molecule that we will inject and that will remain blocked until it reaches the tissue where we want it to act," says the biologist, who led the CRG for fifteen years.

To develop this biotechnological project, named SafeDelivery, Serrano has just obtained an ERC Advanced Grant, one of the most prestigious and competitive research grants in the world for established researchers, endowed with 3.3 million euros.

Only 9% of the proposals submitted by researchers from institutions in the European Union and associated countries, such as the United Kingdom, Switzerland, or Israel, achieve this funding. In Serrano's case, the success is even more exceptional: with this grant, he chains together four consecutive ERC Advanced Grants, an extraordinarily unusual feat that highlights the scientific excellence of his laboratory.

Furthermore, if other grants awarded by the European Research Council are taken into account, such as the Starting Grants, aimed at researchers beginning their independent careers, or the Proof of Concept grants, designed to bring research results closer to the market, the CRG researcher accumulates eight ERC grants.

Catalonia, among the most competitive regions in Europe

The results of this year's ERC Advanced Grants call have been particularly positive for Spain, which has achieved its best participation in history since these grants were created in 2007. With 29 grants, the State occupies fourth place in Europe, only behind the United Kingdom (62), Germany (46), and Switzerland (32), and for the first time, surpasses France (26) and the Netherlands (22).

Of these 29 grants, 14 have been awarded to researchers from Catalan centers and universities, meaning almost half of the Spanish total. Catalonia thus concentrates 48% of all ERC Advanced grants obtained by the State, despite representing approximately 16% of the Spanish population. The 14 grants also equate to 4.4% of the 319 projects funded in this European call, far exceeding Catalonia's demographic weight within the European Union, which is about 1.8%. These figures consolidate the country among the most competitive regions in Europe in attracting excellent scientific funding.

"It is the most direct demonstration of the competitiveness and international recognition of the science produced by our universities and research centers," values the Minister of Research and Universities, Núria Montserrat.

"It shows that Catalonia has a very high level of research, because these projects are extremely competitive," states Eduard Batlle, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona) and one of the world's leading experts in metastatic colorectal cancer. Batlle is, in fact, the other researcher in the State who has managed to secure a third consecutive ERC Advanced Grant and who had previously obtained a Starting Grant.

"We compete with the best in Europe in each discipline, and for the Catalan system to have obtained so many grants in a single call is very meritorious," he assures. "It demonstrates the consolidation of the Catalan research system," adds Serrano.

Deciphering the "superpower" of tumors

In Batlle's case, the European Research Council has awarded him 2.5 million euros to fund the Plastic_CR project for five years, with which he will study how to reduce the adaptability of tumors to become resistant to treatments. He also wants to understand how this plasticity allows tumor cells to escape the tissues where they originate and colonize other organs, causing metastasis, responsible for approximately 90% of cancer deaths.

"It's as if tumor cells could disguise themselves and, with each new disguise, acquire new properties," explains Batlle. "The mutations don't change, but these cells are capable of reprogramming their function and adopting different identities." It is this plasticity, he continues, that allows them to adapt to their environment and do things they would normally be incapable of, such as migrating, generating metastasis, or surviving in conditions of oxygen deprivation. "And when we administer treatments, they are capable of adapting very quickly, even in a matter of hours," he adds.

Over the next five years, Batlle and his team will try to understand the molecular mechanisms behind these transformations and find therapeutic strategies that allow blocking this "superpower" of tumor cells or, even, turn it to their advantage to make them more vulnerable to treatments.

"We know that it is very difficult for a single drug to completely eliminate a metastatic tumor," he explains. "That is why we want to understand how tumor cells change when they are treated and use this information to design therapeutic combinations capable of limiting their adaptability. Our goal is to reduce tumor heterogeneity and increase treatment efficacy."

To achieve this, the team will use organoids, three-dimensional structures obtained from patient samples that faithfully reproduce the biology and heterogeneity of the original tumor. They will also work with animal models of metastatic colorectal cancer and apply single-cell analysis technologies, which allow tracking with extraordinary precision how different cell populations evolve after each treatment.

This project has its roots in Batlle's previous ERC Advanced Grant, dedicated to residual disease. During that research, his team already observed that these residual cells maintained a close relationship with tumor plasticity.

"It was then that we demonstrated that the cells that remain hidden within organs after surgery to remove the primary tumor, and which will eventually give rise to metastases, are capable of changing their identity," he explains.

That Catalonia has obtained 14 ERC Advanced Grants in a single call is not a coincidence, considers Batlle, an opinion that Serrano also shares. These grants, they affirm, are the result of a scientific ecosystem that, after two decades of commitment to talent attraction, internationalization, and competitive funding, has consolidated itself among the most powerful in Europe.