Specific programme: Human Frontier Science Programme

Project RGEC28/2025 has been funded by the Human Frontier Science Programme.

The Human Frontier Science Programme (HFSP) is an international initiative that funds innovative basic research in the life sciences, focusing on transnational and interdisciplinary collaboration to address fundamental biological problems. It supports teams of scientists from different countries to develop novel approaches in ambitious, high-risk projects with no guarantee of success, which individual laboratories would not be able to tackle.

Code: RGEC28/2025

UPV/EHU: coordinator

IP UPV/EHU: Noemí Jiménez Rojo

Project start date: 01/09/2025

Project end date: 31/08/2028

Brief description:

Many living organisms are capable of producing organic crystals inside their cells to fulfill a variety of functions. For example, the compound eyes of certain crustaceans use crystals to amplify their light sensitivity in dim-light habitats. Another well-known example is the chameleon, which takes advantage of the light-reflecting properties of crystals to swiftly alter its skin color.

Therefore, failure to regulate crystal formation properly can be detrimental to tissue and organ function, severely affecting theability of the organism to survive and reproduce. The zebrafish, a vertebrate model organism, also produces crystals that play a key role in pigmentation. These are formed within specialized cells called iridophores, inside dedicated subcellular compartments, or organelles, known as iridosomes. Here, control of crystal size, shape, and assembly take place with a precision that currently far exceeds our abilities to grow such structures synthetically. In the proposed study, we plan to uncover how this process occurs, considering an essential, but so far unexplored, structure: the lipid membrane that encloses each crystal inside the cells. We want to understand which molecules are found at the iridosome membrane, their biochemical nature, and to what extent those can contribute to such exquisite crystal formation. For this purpose, we will apply a highly interdisciplinary approach combining cutting-edge techniques from molecular biology, such as CRISPR-Cas9, with biochemistry, like mass spectrometry, and molecular modeling We will make use of novel chemical biology methods to measure and manipulate iridosomal membrane biophysical properties and track protein function in vivo in zebrafish, and in iridophore cell cultures. The data obtained will inform us on how to generate and reconstitute synthetically a biomimetic system able to produce crystals at scale and morphology to those of zebrafish, using a combination of biological and chemical transformations under physiological conditions. We expect that the results we obtain will facilitate the development of therapeutics to treat diseases where aberrant crystallization occurs, such as kidney stones and gout. In addition, they will contribute to new protocols to synthesize organic crystals for a variety of applications in the areas of optics and material science.