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Spanish science, crossing borders: Dr Rafa Luján

23 Jun 2021 8:00 am - 23 Jul 2021 5:00 pm

The Institute for Research in Neurological Disabilities (IDINE, Faculty of Medicine of Albacete, University of Castilla-La Mancha) focuses on the study of motor, sensorial and cognitive neurological disabilities. It has 13 research groups on basic, clinical and translational studies, but including also social and legal aspects of disabilities.

The Synaptic Structure Laboratory, directed by Dr. Rafa Luján, is located inside the IDINE. Dr. Luján, Professor of Histology and director of the IDINE research group, focuses on understanding the basic mechanisms of brain functions, specifically through cellular and subcellular analysis of neuronal signalling processes. His main work understands the process of synaptic transmission mediated by receptors for neurotransmitters and ion channels in normal and pathological conditions.

Dr. Luján kindly opens the doors of his lab to the Office of Cultural and Scientific Affairs of the Spanish Embassy in the United Kingdom. 

  • You started your career in Biology to move later into a School of Medicine. Could you tell us a bit more about your career path and about the reasons that made you be interested in Science and in this specific field of research? 

Since I was a kid, maybe because I lived by the sea, I became interested in Biology. One of the gifts I loved the most was a small light microscope that I used since I was 10 years-old to visualise all type of microscopic animals and plants. After finishing secondary school, I moved from my home city, Almeria, to Granada to study at the Faculty of Biology in the University of Granada. Following my graduation in 1990, I started my PhD studies at the Department of Cell Biology to understand how administration of ethanol affects the number and structure of nerve cells. At this time, I became fascinated about the brain and its complexity. I completed my thesis in 1993 and received Ph.D. Then, I moved to the University of Oxford, where I worked as a Postdoctoral Researcher for about five years at the Laboratory of Prof. Peter Somogyi, the Director of the prestigious MRC Neuroanatomical Neuropharmacology Unit. At that time, this was the leading and most important laboratory in the application of high-resolution immunoelectron microscopy to study the brain. Since then, I have applied this methodological approach to understand how neurons work under normal and pathological conditions. In 1998, I returned to Spain to spend two years at the “Instituto de Neurociencias” of Alicante, and them I established my independent research group in the Medicine School, Universidad de Castilla-La Mancha, where I setup the Laboratory of Synaptic Structure. My fascination to visualise objects that are too small for the naked eye, combined with my curiosity to unravel the complexity of the body organs like the brain, always drove my interests to the use of light and electron microscopes applied to the study of the function and dysfunction of neurons.

  • Can you explain what your main lines of investigation are, particularly in the field of Alzheimer’s disease?

Our research interest has always focused on unravelling the functional structure of neurons, with particular emphasis in dissecting the molecular architecture of neurons through the analysis of cellular and subcellular localization of functional and structural molecules.

This type of information is crucially important to understand the basic mechanisms by which the brain functions and, therefore, the consequences deriving from its dysfunction under pathological conditions.

Particularly, our ongoing research lines are seeking to reveal the structural, molecular and functional heterogeneity of central synapses (the key elements for neuronal communication). We try to establish the subcellular localization of neurotransmitter receptors and ion channels, two main families of proteins involved in the function of synapses and neurons) along the neuronal surface, and to define the molecular and cellular mechanisms underlying pathological conditions in neuronal signalling, including Alzheimer´s and Parkinson´s diseases.

To achieve these goals, we use imaging techniques that allow us to visualise any molecule that is present in neurons with a high spatial resolution. We combine these techniques with specific software to perform 3D reconstruction of the neurons and quantify their molecules in physiological conditions and how they change in pathological conditions.

  • Your team was praised for being the first international group applying FIB/SEM technology for your research. Could you explain what that is and how is that important for your work?
The FIB/SEM technology was developed at first for material research applications and it applied only to the study of biological samples around 2008. Our improvement on Neuroscience has been to combine conventional immuno-electron microscopic techniques with FIB/SEM to obtain a large volume of images
and to provide for the first time a tri-dimensional view of the molecules that are essential for the communication between neurons in the brain. In addition to this method, that we call immuno-gold FIB/SEM, we also employed the freeze-fracture (SDS-FRL) technique, a powerful tool for determining the macromolecular structure of neurons. It consists of physically breaking a frozen biological sample to reveal external and internal structures, thus providing a unique view of neurons not possible to achieve with other techniques. When this technique combines with visualization of specific molecules, it provides unprecedented insights into the role of these molecules in physiological and pathological conditions. The data we created are been used by other laboratories in simulations and algorithms that reconstruct synaptic connections for use in human brain models.
  • IDINE has also created an important software for quantification of nanoparticles in microscopy images. What is the importance of this software? How does it affect our understanding on how neurons work? 

All the merit should go to a group of talented computer engineering scientists who in collaboration with our research centre developed the new software. The novelty is that this software allows us to quantify automatically those molecules under study using immuno-gold FIB/SEM and SDS-FRL techniques obtaining data as fast as simply by clicking a key. The advantage of the software is that it can measure many parameters like distance between molecules, formation of clusters of molecules, composition of these clusters, abundance of molecules in different compartments of neurons, etc. This large amount of data generated with the software became available to other laboratories and used in algorithms to simulate how specific brain regions works.

  • The research group that you lead has a very international approach, participating in multiple European projects and other international partnerships like the Human Brain Project in collaboration with Japanese institutions. What are the benefits of having this international approach? How can Science benefit from it?

The classical stereotype that scientists are people working isolated in a laboratory built in the basement of a house is simply very far from reality. Behind every scientific article published or line of research there is a large team of people. Given the difficulties in Spain for working in Science, with low and limited funding and young scientists looking for jobs abroad, scientific collaboration is more important today than it was decades ago. I have always tried to make efforts for collaboration with other institutions that bring together researchers with diverse scientific backgrounds or expertise. In my case, researchers from different labs and countries bring their own specific expertise and skills. In general, solving complex problems and addressing new scientific questions that benefit from a multidisciplinary approach are critical steps in Science. Without these multidisciplinary efforts, our scientific contribution to European projects like the Human Brain Project would have been much more difficult.

  • In light of the impact that Covid-19 has had in the overall society, do you think we will see a shift in attitudes towards the public view of Science? What prospects do you expect for the future?

There’s no arguing about one thing: only the funding and all the efforts put in Science gave rise to the development -in record time- of several safe and efficient Covid-19 vaccines that are currently in use. People are now perfectly aware of the importance of Science and for the first time the media of our country promoted campaigns in favour of increasing investment in Science. Therefore, Spanish people have a very positive attitude towards Science and are aware of the benefits of investing in Science. The problem in Spain is not about people but politicians and political parties, more worried to keep their jobs and to increase their votes than to look for the wellbeing of society. In other countries, including many in Europe, this is no longer a problem. They have learned that investing in Science is critical for social and economic progress. Investing in Science means investing in the future. Those countries that do not follow this simple rule will stay well behind.


23 Jun 2021 8:00 am
23 Jul 2021 5:00 pm
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Embassy of Spain
see main text, United Kingdom