El Desarrollo del Fenotipo

We use modern quantitative cell biology approaches to decipher the full function of the most enigmatic role of telomeres in the cell: the formation of the telomere bouquet in meiosis. This 3D conformation has captured the attention of cell biologists since the 19th century when it was first observed, and its function, despite having been conserved since the origin of eukaryotes, remains a mystery. Our aim is to understand the telomere bouquet formation as one of the main drivers of genetic diversity

​Understanding how cells interact and interpret dynamic signaling to create precise spatial patterns during embryonic development is one of the central questions in developmental biology, fertility research, and regenerative medicine. While answering this directly in humans presents technical and ethical challenges, new tools in stem cell research and bioengineering have opened a window into quantitatively answering these questions in vitro. By integrating these methods with mathematical modelling, such as a novel mathematical and statistical framework we developed inspired by the Waddington landscape metaphor (Camacho-Aguilar E, Warmflash A, Rand DA, PLoS Computational Biology 2021, Saez M, Blassberg R, Camacho-Aguilar E et al, Cell Systems 2022), our lab aims to gain deeper insights into human development. We are dedicated to merging stem cell research and mathematics to enhance our understanding of development. Some topics we are interested in are: dynamic signalling interpretation, cell-cell interactions, patterning, and mathematical modelling of cell fate transitions.

The Applied Systems Biology team is a part of the Bio2Eng group at IIM-CSIC. Our primary objective is to elucidate the interaction between biological systems and the environment, specifically the dynamics responses to environmental stress and the presence of other species. We use a multiscale modelling approach that spans from biochemical networks to ecological interactions between species.  These models provide fundamental knowledge of how biological systems behave, which can be leveraged to optimize biological systems and bioprocesses of industrial interest to produce novel, high-quality, and sustainable products. In this concern, we also develop methods and tools for modelling, systems design and optimisation. We are currently considering several applications, including the dynamic modelling of food fermentation processes led by single or multiple microbial species and the modelling and design of multi-trophic aquaculture systems.

My main research goals are focused on understanding the role of the microenvironment in the progression of several tumors and cardiovascular diseases as well as on the development of microfluidic devices for cell culture applications (Organ on Chips).

My interest lies at the intersection of Ecology, Evolution and Developmental Biology.
My group is specifically focused in understanding how organisms alter their phenotypes in response to changing environments and the extent to which such environmentally-induced changes in development influence trait evolution. The phenotypic responses we study range from responses to abiotic factors such as temperature or hydroperiod, to biotic interactions with predators, competitors or parasites, and include both within-generation and transgeneration responses.

Lines of investigation:1. To delineate the role of lipid sensors and solute transporters for amino acids and
their effectors in the precise control of the juvenile-to-adult transition. 2. To study the processes of secretion and ribosome maturation in PG cells in vivo. 3. To define the secretome of PGs and study how it controls the growth of peripheral organs.

A major aim of the Cell Cycle and Signaling group is to contribute to the understanding of how protein phosphorylation is able to regulate the assembly, localization and activity of macromolecular complexes. Focusing on the cell division cycle, we study how the modification of a few specific residues of a given protein at defined subcellular locations and/or cell cycle times can dictate its structure and partners. Furthermore, we explore how this ultimately results in changes in the activity and/or localization of different macromolecular assemblies (i.e. protein motors, microtubule-nucleating complexes) and the cellular structures/machines to which they contribute (i.e. the centrosome or the mitotic spindle).

My group studies how cell lineage determines the generation of neuronal diversity in the cerebral cortex. We aim to discover molecular mechanisms that act sequentially to produce specific neuronal types. We also implement new technology to mimic the natural cell specification processes to generate specific neural types on demand.

Our group is interested in understanding the molecular and cellular basis of organ formation during embryonic development. This knowledge is important for identifying the origin of congenital malformations and to understand the basis of morphological evolution. We use animal models (mouse and chicken embryos) to address several biological questions related to development, such as cell morphogenesis and differentiation. We also study the role of signaling pathways in development, adult tissue homeostasis, inflammation and regeneration. 

We are interested in the principles that govern higher-order growth control, as illustrated by the perfect symmetry of the body and proportionality between body parts. Central to this control is a body metric or body schema mechanism in the brain that compares actual size to expected size (by age and genetics), detects mismatches, and corrects for variations. Growth control is also vital at the local level, and one manifestation of the failure of this control is cancer. We leverage juvenile and adult-stage (gut) Drosophila cancer models to uncover the intricate pathways of cancer initiation and escape from innate antitumor immunity to safer and longer-lasting therapies. We also use population genetics and genomics to unravel individuality and resilience using fruit flies.

In our laboratory, we are interested in understanding the molecular and cellular mechanisms underlying cell migration and epithelial morphogenesis. Cell migration plays a key role in a wide variety of biological phenomena that take place during both embryogenesis and in the adult organism. Both during development and in the adulthood, cells can move individually or collectively. In addition, they can use as substrate for their movement either extracellular matrix (ECM) components or other cells. Finally, cell migration, a fascinating process in normal cells involving numerous intricately coordinated and controlled processes, becomes destructive and damaging when acquired by cancerous cells. In our lab, we use the migration of the border cells (BC) and the follicular epithelium (FE) of the Drosophila ovary as simple genetic systems for the in vivo study of the mechanisms regulating cell migration. In addition, we use the Drosophila wing disc as an attractive system to study individual cell invasion. Shaping tissues and organs requires forces with proper directionality, generated by the contraction of actin filament (F-actin) meshworks by the molecular motor Myosin II. The magnitude, direction and timing of contractile forces depend on the organization of the cellular actomyosin meshworks and how these networks are connected between cells and to the extracellular matrix (ECM). In the lab, we are interested in understanding the mechanisms by which basement membranes (BMs) -specialized ECM that surrounds most organs and tissues- contribute to the generation of cell and tissue shape by providing a physical scaffold to oppose the contractile forces generated by epithelial cell shape changes.

Discrete mathematical models for the topological analysis of data, with special interest on biological data

We use the formation of epithelial tissues, with a special focus on the analysis of the embryonic tracheal (respiratory) system of Drosophila, to investigate the general mechanisms of organ and tissue formation, and in particular the mechanisms of morphogenesis of branched tubular structures (tubulogenesis). Our current projects address the genetic, cellular and molecular mechanisms that govern the formation and the homeostasis of the epithelium, focusing on the following issues: 1) Interactions tissue/environment during organogenesis; 2) Contribution and remodelling of Adherens Junctions and cell polarity in epithelial morphogenesis; 3) Spatiotemporal coordination of the cellular mechanisms underlying the morphogenesis of the tracheal system

Beyond novel and optimized CRISPR-Cas approaches in zebrafish, we use molecular and cellular biology, functional genomics to better understand early vertebrate development and human diseases. In particular, we are interested on a fundamental biological process, the maternal-to-zygotic transition (MZT). The MZT is a complex cellular reprogramming event in vivo driving the beginning of a new life. During the MZT, the maternal contribution (mainly RNA and proteins) is responsible for transcription activation in the embryo whose genome is initially silenced. After that, this maternal contribution is eliminated in a controlled manner. Despite recent advances, the molecular mechanisms that trigger and orchestrate early development and the MZT are not yet fully understood. Therefore, our lab is also interested in uncovering new regulatory factors controlling early development that will help to better understand cell reprogramming in vivo.

My goal is to study the functional organization of cells at the molecular level using computational approaches. I study the functions and interactions of proteins and chemical compounds in the cell from a systems biology perspective. I’m specially interested in the study of cellular dysfunctions that lead to human disease.

Our research focuses on the aetiology and prevention of two neuropaediatric diseases that cause death and disability in newborns and are often associated with motor, sensory and cognitive impairment: neural tube defects and perinatal stroke. The common factor in these diseases is the existence of structural damage to the developing central nervous system. Currently, there is no cure for these neuropaediatric diseases causing high morbidity. Adequate supply of nutrients from the maternal diet is crucial for the proper development of the embryo and neonate. One strategy that has proven to be efficient in the prevention of neuropaediatric diseases is supplementation through the maternal diet, such as folic acid to prevent NTDs. In our laboratory, based on the use of mouse models, we study the molecular and cellular basis of these diseases, in order to design strategies for prevention or neuroprotection through maternal dietary supplementation. In parallel, and with the idea of translational research, we are looking for biomarkers for the early detection of neonatal stroke in both mouse and human models.

We are studying the genetic basis of the control of axillary bud development in the model system Arabidopsis, and in the crop species tomato and potato in which control of lateral shoot branching is of great agronomical interest. We have characterised the Arabidopsis BRANCHED1 (BRC1) gene, which acts as a central switch of axillary bud development and outgrowth. We are now expanding our knowledge of the genetic networks involving BRC1 in Arabidopsis.

Our group seeks to unravel the mechanisms that underlie a wide variety of neurological pathologies, in particular neurodegenerative and oncogenic disorders, which have in common an alteration in mitochondrial function. To explore how they occur, we study the interplay between the morphology, ultrastructure and dynamics of these organelles in the regulation of metabolism, respiration, redox status, and neural bioenergetics. We focus our main interest on the coordination of mitochondrial function between cells and tissues, through intercellular transfer of mitochondrial content. Our research plan is based on these central axes: i) Mitochondrial dynamics, metabolism and bioenergetics: We study the dynamic changes in mitochondrial morphology, ultrastructure, transport and functionality. Dissecting the molecular actors that orchestrate these processes is key to address their genetic and pharmacological modulation, thus providing therapeutic benefit in neurological diseases. ii) Intercellular communication and mitochondrial exchange: Intercellular mitochondrial communication and traffic, particularly through membrane nanotubes or tumor microtubes, has been shown to be key to preserving the proper functioning of the nervous system. We address these communication processes at the molecular level, as well as the acquisition of free mitochondrial content or as in included in microvesicles. Our objective is to describe the mechanisms by which mitochondria and intercellular communication lead to neurodegenerative processes or oncogenic progression in the nervous system. iii) Mitochondrial transfer and morphofunctional reconfiguration: Intercellular transfer allows healthy mitochondria to integrate into the host cell network. Likewise, the transmission of damaged organelles for surrogate degradation or mitophagy in neighboring cells is equally possible. Addressing how any forms of transfer reconfigure metabolism and bioenergetics, to define the physio(path)ology of the nervous system, represents for us a key objective towards new therapeutic approaches.