Research

The complex interplay between physics and the intricacies of life is a captivating and cutting-edge scientific area. Here, you can explore some of the projects I am currently involved in or have been a part of, investigating the fascinating world of biophysics.

Pattern Formation and Emergence in Biology

Project as principal investigator: Pattern Formation a unifying framework.

During embryonic development, groups of cells are organized creating patterns to give rise to tissues and organs. Experimental discoveries have unveiled a plethora of mechanisms underlying pattern generation, ranging from molecular pathways to different transport processes. However, pattern formation may not be confined to specific pathways or transport mechanisms.

The vast number of proposed mechanisms and models may seem overwhelming, suggesting that pattern formation is highly specific to each animal model, tissue type, transport mechanism, or morphogen molecule. However, some findings indicate that a unifying formal description is possible. For example, cellular channels, called cytonemes, are prevalent across the main signaling pathways, delivering signaling molecules and vesicles via filopodia-like structures, regardless of the biochemical differences between morphogens. This suggests that evolution has converged on common strategies to generate patterns despite biochemical and tissue specific constraints. Supporting this idea, we have shown in previous studies that cytoneme signaling and diffusion-based mechanisms can produce similar patterns (Aguirre-Tamaral et at. 2021) and may be formally described with similar equations, implying that evolution focuses on the emergent pattern rather than the specific formation mechanism. 

Currently, I am the PI of a project to address this biophysical research of pattern formation. By unraveling common principles underlying diverse mechanisms, we want to establish a unified formal equations for understanding pattern emergence, where the specific mechanism would be special cases of a unifying framework.

Morphogen signaling, development and guidance mechanism

Previous project in collaboration with the Severo Ochoa Molecular Biology Center (CBMSO) and the University of Granada

Cell-cell communication is crucial to coordinate cell behavior during organism development, especially in the generation of differentiation patterns via morphogen gradients. Morphogens are signaling molecules secreted by a source of cells that activate target cells in a concentration-dependent manner. 

Cell-cell contact via filopodia-like-structures (Cell channels called cytonemes) has been discovered as a mechanism for the gradient formation of the main signaling morphogens. Despite of the advances in the understanding of cytoneme signaling, little was known about how cytonemes navigate through the extracellular matrix and how they oriented to find their target. 

Using Drosophila as a experimental system, we discovered in Hedgehog (Hh) signaling pathway that cytoneme stabilization and orientation depend on the relative levels of Hh co-receptor and adhesion protein Interference hedgehog (Ihog) and the glypicans Dally and Dally-like-protein (Dlp) (Fig. 2, 3, 4).

We developed a biophysical model to study and corroborate mathematically this cytoneme guiding mechanism. Our results and simulations probed that the relative levels of Ihog and Glypicans molecules can acts as guidance factors in an attractive and repulsive manner to control the cytoneme guidance (Fig. 4,5).  (Aguirre-Tamaral et al. 2022)

Origin of Life: A Complex System approach

RNA proto-replication project in collaboration of Dr. Jacobo Aguirre Group and Dr. Carlos Briones at Center of Astrobiology (CAB, Spain)

How the first RNA replication took place on the early Earth? Combining Complex Systems theory, mathematical modeling and RNA biochemistry we wanted to study this open question of critical importance in astrobiology and the origin of Life. 

A hypothesis for the origin of life strongly supported by experimental data is the RNA world, which suggests that life was originated in an environment in which RNA molecules were able to self-replicate (through RNA ribozymes). However, the minimum size for an RNA polymerase ribozyme is ∼165 nt, 3-4 times longer than what is attainable through abiotic, random polymerization of RNA. This limitation could be solved if a modular evolution of RNA was achieved. In this model, the RNA ribozyme appeared thanks to a stepwise process, in which (i) short (< 40 nt) RNA molecules polymerized abiotically from single nucleotides, (ii) folded into their minimum free energy structure, (iii) some of them were endowed with RNA ligase activity and catalyzed the assembly of larger RNA molecules, and (iv) generated a functional RNA ribozyme.

However, such a hypothesis leads to the difficulty of obtaining many identical copies of a specific RNA sequence, a critical requirement for the emergence of effective RNA replication. This is the challenge that we want to address. Therefore, we use computational models to study the possible first replication of RNA molecules located in an adequate environment of the early Earth (e.g. the interphase aqueous solution-clay, Fig. 6A). Our model simulations allow to study RNA replication under different environmental conditions (β, Fig. 6B) and to analyze the RNA copy fraction over time (Fig. 6C).

Our biophysical model can be used as an in silico tool to identify and study how the efficiency of the RNA replicative phenomenology depends on the parameters of the system, such as the RNA length, size of genetic alphabet, strength of chemical bonds and probability of rupture, environmental conditions, etc. (Alejandre, Aguirre-tamaral et al 2025).

Microbiome and bacterial community network

Microbiome Project in collaboration of Dr. Jaime Iranzo Group at Centre for Plant Biotechnology and Genomics (CBGP, Spain)

Microbial communities, known as microbiomes, are everywhere in nature: in the environment, in our food and even in our bodies. They play an important role in ecosystems and also influence our health. Understanding the physical and chemical interaction network of microbiomes under different conditions is therefore a key objective for academic and medical reasons. For example, the causes underlying sudden changes in microbiome composition under pathological conditions in human microbiome still have several open questions, such as the effect of microbial order of cooperation on health.

One of our focus is understand the intestinal cooperative network in different environments and pathological conditions, reconstructing metabolic models from human intestinal microbiome in patients with inflammatory bowel disease (HMP2). We incorporate the diverse metabolic capabilities of individual species and simulating their potential interactions. using flux balance analysis to compute the cooperation of reconstructed and curated  metabolic models of microbial communities.

Our results provide insights into the composition of the microbiome in different media and contribute to a deeper understanding between health and microbial interactions in the gut ecosystem.

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