Scientists have long been fascinated by the complexity and adaptability of living organisms. Now, a groundbreaking project involving Jordi García-Ojalvo, full professor from the Department of Medicine and Life Sciences (MELIS) at Pompeu Fabra University, and coordinated by Dr Aneta Koseska at the Max Planck Institute for Neurobiology of Behavior (MPINB) – caesar in Bonn, Germany, has been awarded an ERC Synergy Grant of €11.2 million to take it forward. The aim of the project is to uncover an astonishing concept: that single cells are capable of learning from their environment. This ambitious research initiative has been recognized with a prestigious ERC Synergy Grant for Dr Aneta Koseska; professor Jordi García-Ojalvo, from UPF; professor Dietmar Schmucker, from the University of Bonn; and professor Jeremy Gunawardena, from Harvard Medical School. The €11.2 million grant will provide significant funding for this team to explore how single cells create internal representations of the external world.

According to UPF professor Jordi García-Ojalvo, “in the same way as the brain internally represents the information it receives from its environment in its neural networks, a cell can do the same with its networks of genes and proteins. This gives single cells a substantial ability to process information”, adds professor García-Ojalvo.

“We believe that cells are not just passive entities executing pre-defined programmes”, says Dr Koseska, head of the Lise Meitner Research Group on Cellular Computations and Learning. “Instead, they actively process information, form internal models of their surroundings and use these models to make context-dependent decisions, much like learning”.

Diverse model organisms to uncover universal mechanisms

The research will focus on a broad range of model organisms, including bacteria such as Bacillus subtilis, unicellular eukaryotes like Paramecium and Tetrahymena, neuronal cell culture models and neurons within the brain of the fruit fly Drosophila melanogaster. By studying these systems in a comparative manner, the team aims to identify generic molecular mechanisms through which single cells learn.

Genetic network of a human cell. Photo: UPF
 

“By examining such a diverse set of organisms, we hope to uncover fundamental principles that govern learning at the cellular level”, explains professor Jordi García-Ojalvo. “This comparative approach allows us to identify mechanisms that are conserved across different life forms, providing a unifying framework that links various areas and scales of biology”.   

From single cells to complex nervous systems

One of the most ambitious goals of the project is to understand how single neurons during the development of the brain learn to form, stabilize or eliminate axonal branches. This process generates stereotyped synaptic patterns under highly variable conditions. By gaining information about these mechanisms, the team aims to address fundamental biological questions about how learning and memory are established within cells.

“Understanding how neurons make precise connections is essential for deciphering the functioning of the nervous system”, remarks Dr Schmucker. “We want to find out how individual neurons learn to form these connections despite the complexity and variability of their environment”.

Formulating a comprehensive theory of cellular learning

The interdisciplinary team of scientists brought together by the project, entitled “CeLEARN: Learning in Single Cells Through Dynamical Internal Representations”, has a combined expertise that includes information theory, dynamical systems, cellular biology and neuronal development.  

Over the next six years, the CeLEARN project will capitalize on the synergy of its international consortium to push the boundaries of what we currently know about cell behaviour. By examining the various model organisms in a comparative manner, the team aims to identify the core internal representations and the universal molecular mechanisms that make single-cell learning possible. This may shed light on fundamental principles that apply to the entire tree of life, from bacteria to the neurons that form networks during the development of the brain.

Looking to the future

The knowledge gained from the CeLEARN project is expected to represent a major step forward in our understanding of how cells learn and adapt. By identifying the molecular mechanisms underlying single-cell learning, the research could pave the way for innovative therapies for diseases rooted in cellular dysfunction and contribute to the development of new technologies that harness the learning capabilities of cells.