Laura Pérez-Chirinos, Roger Castells-Graells (centre) and Pablo San Segundo. Crédito: Laura M. Lombardía / CNIO
The National Cancer Research Centre (CNIO) establishes a Biomolecular Design and Structural Nanomedicine Group, led by Roger Castells-Graells
The goal is to create protein nanoparticles that are useful in earlier cancer detection and to accelerate the development of more effective drugs with fewer side effects
Castells-Graells has returned to Spain from the University of California in Los Angeles (USA)
Proteins are complex molecules that perform crucial functions in the body. Knowing them is essential to understand and try to cure diseases: if we know the three-dimensional structure of a protein involved in cancer, for example, we can try to design a molecule capable of modifying that protein in order to treat that cancer.
The Biomolecular Design and Structural Nanomedicine Group has just joined the National Cancer Research Centre (CNIO) with the aim of advancing this type of strategy through the use of ‘synthetic proteins’. Roger Castells-Graells, who heads up the group, explains that they use “artificial intelligence to design nanoparticles formed by synthetic proteins, molecules that mimic the shape and structure of natural proteins and which are given specific functionality.”
His team, which also includes Laura Pérez-Chirinos and Pablo San Segundo, designs nanoparticles using computational tools and then validates their biological functionality experimentally in the laboratory. These nanoparticles are applied to the visualisation of biological processes, diagnosis and drug development.
Graells, Pérez-Chirinos and San Segundo have joined CNIO as part of the Building the AI Generation programme, within the Generation D initiative, promoted by Red.es.
Microscopic tags to make molecules visible
Some proteins involved in tumour processes are so small that they are undetectable even for the most advanced techniques, such as electron cryomicroscopy, which is used to see molecules at very high resolution. “We have developed nanoparticles that bind, as tags, to certain small proteins, and mark them to make them detectable,” says Castells-Graells.
Being able to see them in tissues or organs can help detect changes that are typical of a tumour, which can help advance the diagnosis of certain cancers.
Evaluation and development of possible drugs
These ‘molecular tags’ can also accelerate drug development. A previous research paper by Castells-Graells, published in the prestigious scientific journal PNAS, dealt with the creation of one of these nanoparticles designed to bond with the KRAS protein – involved in 25% cancers – while interacting with a specific drug. The nanoparticle allowed the team to study which parts of KRAS bind to the compound, which is essential when seeking to understand the mechanism whereby a drug takes action, to make this drug more effective.
“This nanoparticle has sparked the interest of pharmaceutical companies, because it allows us to analyse many more drug candidate molecules in a shorter space of time. A study that might have taken years before, we can now do in weeks,” says Castells-Graells.
The intention is to design markers to detect proteins in living cells. “Our long-term goal is for this technology to be applied to patient tumour samples,” explains Castells-Graells.
Music, botany, cancer research
“When the opportunity arose to come to CNIO, for me it was a very clear option,” recalls the biotechnology researcher, who previously worked at the University of California, Los Angeles (USA). “CNIO spearheads international research into various types of cancer, with so many groups to establish synergies with in order to develop and test our technologies. Óscar Llorca, director of the Structural Biology Programme at CNIO, is a huge name in the study of proteins by electron microscopy.”
Roger Castells-Graells (Sabadell, 1993) studied Biotechnology at the Autonomous University of Barcelona (UAB), also completing research stays in Zurich (Switzerland) and Munich (Germany). He combined these studies with a Degree in Music specialising in oboe and saxophone performance. After graduating, his interests in both molecular biology and botany led him to pursue a PhD in Biochemistry at the John Innes Centre in Norwich (UK), a leading research centre in the study of plants and microorganisms.
From plant viruses to nanoparticles for biomedicine
While researching plant viruses during his PhD, he began working with protein nanoparticles, and wondered: “could we design new nanoparticles inspired by the structure of plant viruses, to develop treatments? We would be applying what we learn from these viruses to something useful for humans,” he says.
At that time, he heard Todd Yeates, University of California Los Angeles (UCLA) researcher, talk about his computational methods for protein design. So Castells-Graells joined Yeates’s laboratory to carry out his postdoctoral degree. There he developed his knowledge and skills in artificial intelligence, biophysics and computational biology, which allowed him to design nanoparticles to apply to the study of cancer.
He says that “both the interdisciplinary vision I have acquired along the different phases of my career, as well as internationalisation, are fundamental to my work at CNIO. My goal here is to integrate all those tools to develop solutions that contribute to the treatment of diseases.”
An opportunity for Generation D.
The Building the AI Generation programme, which has made it possible for Castells-Graells to return to Spain and hire his team, is part of the Generation D initiative, promoted by Red.es, an initiative attached to the Spanish Department for Digital Transformation and Public Service through the State Secretariat for Digitalisation and Artificial Intelligence.
With a budget of 120 million euros, the Building the AI Generation programme has overseen the funding of 374 research contracts in the area of artificial intelligence and digital transformation in all scientific and research fields. Its actions are financed by the Recovery, Transformation and Resilience Plan through the Next Generation funds of the European Union, within Investment Framework 4, Component 19 of the National Digital Skills Plan.