We just published a paper in PNAS in which we describe in mice which specific neurons transmit the signals that cause this discomfort.

In this article, which is a collaboration with the University of Washington, we analyzed the cells of the vestibular nuclei of mice subjected to short and repeated rounds of spinning, and demonstrated the importance of neurons that express the VGLUT2 protein in motion sickness symptoms.

These neurons are required for rotation-induced effects of motion sickness, such as decreased appetite, lower body temperature, reduced locomotion, and conditioned taste avoidance (aversion to a taste introduced close to the time of spinning).

Blocking them by chemogenetics (molecules specially designed to interact with these specific cells) prevents motion sickness in mice subjected to spinning. And also that their activation by means of a beam of light (optogenetics) in still mice reproduces the same symptoms of dizziness as when they are subjected to rotation.

Specifically, we identified a subgroup of VGLUT2 neurons that express the cholecystokinin gene (CCK-neurons) as being responsible for the effects of motion sickness by sending signals to an area of the brain called the parabrachial nucleus, responsible for generating unpleasant sensations.

The mice to which we administer a drug that blocks the CCK-A receptor have less activation of the parabrachial nucleus and have less motion sickness symptoms. Common anti-motion sickness drugs target the histaminergic system, causing drowsiness. CCK-A receptor blocking drugs, which are already approved by the American and European Medicines Associations (FDA and EMA) as a treatment for gastric problems, are safe and do not have this unwanted effect, so they would be an excellent option to treat motion sickness.

In future studies, we want to further define the contribution of these neurons to other types of dizziness to advance in the approval of drugs that block the CCK-A receptor as a new therapy against this discomfort.

Article: Pablo Machuca-Márquez, Laura Sánchez-Benito, Fabien Menardy, Andrea Urpi, Mònica Girona, Emma Puighermanal, Isabella Appiah, Richard D. Palmiter, Elisenda Sanz and Albert Quintana. «Vestibular CCK signaling drives motion sickness–like behavior in mice». October 17, 2023. PNAS. https://www.pnas.org/doi/10.1073/pnas.2304933120

The Agencia Estatal de Investigación announced the provisional list of researchers awarded with a Ramon y Cajal contract and we are extremely happy as Laura Cutando has been selected. The purpose of this grant is to promote the incorporation of researchers with an outstanding career into research organizations, so that they acquire the skills that will allow them to obtain a stable position in a research organization of the Spanish Science System.

The main line of her research will be focused on studying the genomic and functional alterations taking place in specific cell populations of the cerebellum in mental and neurodevelopmental disorders such as Rett Syndrome. Through the combination of cell-type specific omics, gene editing tools, mouse models, and behavioral, histological, and molecular studies, she aims to identify potential therapeutic targets to ameliorate cerebellum-dependent symptoms observed in these diseases.

We are so proud of her! Huraaa!

(Thanks to Marta Luna for the image. Always the best meme maker)

Emma, Albert and Eli filed the application to the European Medicines Agency (EMA), which has recently designated this compound as an orphan drug for the treatment of a rare disease.

To facilitate the development and authorization of drugs for rare diseases, regulatory agencies can give certain medicines the designation of orphan drugs, which gives them several incentives.

Leigh Syndrome is a very severe neurodegenerative mitochondrial disease that affects the pediatric population. Because mitochondria do not work well and there is a lack of energy, patients have problems in many organs and systems, but mainly in the muscles and nervous system, which are the ones requiring most energy. In an extensive preclinical study combining the use of animal models of the disease with patients-derived cells, researchers of our group have shown that cannabidiol exerts multiple beneficial effects. Among them, they found a decrease in the production of oxidative stress and inflammation, an improvement in social and motor problems, a reduction in epilepsy and an increase in life expectancy in Leigh syndrome mouse models.

“We hope to be able to conduct soon a clinical study on the use of cannabidiol in patients”, explains Emma, one of the leaders of this study. In order to facilitate development steps, they have just obtained an orphan drug designation by the European Medicines Agency, which entails several benefits such as scientific advice and assistance in protocols, market exclusivity and reduced development costs, among others, with the ultimate goal of providing an effective drug for the treatment of this devastating disease.

One more time, we celebrated a calçotada at Andrea’s grandparents’ house, in a small village of El Penedès.

Old, new, and who knows if future (!) generations of Quintanalab members were reunited for the best of the reasons: eating calçots until our bodies complained.

Although it was a team game, Alex was the main cheff, with the help of his son Luca.

We ate (a lot!), played board games, and enjoyed the time together somewhere nicer than in the lab (although we do like labs).

Quintanalab members are the best <3

Already waiting for next year’s!

Last Friday, within the Brain Awareness Week, Laura Cutando gave a talk to 9-year-old students from Escola Enric Grau i Fontseré, in Flix.

It was the end of a series of workshops, organized by the INc-UAB communications department and the educational cooperative Eduxarxa, in which students discovered the nervous system.

In the talk, Laura told them how it is like to work in a lab and showed them some of the experiments they can do to test the memory and motor skills.

Who knows if some of them will become neuroscientists one day!

We have great news! The European Research Council awarded Albert with a Proof of Concept grant to work on ResisCHIP, a kit we are developing to quickly detect antimicrobial resistance (AMR).

AMR causes over 700.000 deaths each year and is associated to reduced quality of life, increased hospitalization periods and medical costs. Hence, developing fast diagnostic methods to identify the optimal treatment is key to effectively fight AMR and increase survival rates of patients encountering life-threatening infections. So far, diagnostics rely on bacterial cultures, leading to slow turnaround times, which are linked to the preventive administration of broad-spectrum antibiotics, often inefficient and leading to worse disease outcomes and spread of AMR. Novel approaches such as DNA PCR-based diagnostic panels or next generation sequencing methods have been recently proposed to address this issue. However, they are target a limited number of pathogens and genes or require expensive equipment and highly-trained personnel. Furthermore, they require a culture step to reach detection levels, usually lasting a few hours, that can be critical for serious conditions.

Recently, using technology derived from ERC StG and PoC grants, we designed a method to concentrate, purify, and isolate bacterial RNA in just 5 minutes. With this grant, we seek to develop and validate these tools, combined with a rapid RNA chip array with single-molecule resolution, to provide a culture-free, fast, and highly sensitive alternative to bacterial infection diagnostics from direct blood samples.

Once developed, ResisCHIP will provide a tailor-made diagnostic kit with the capacity to identify thousands of genes and pathogens from a blood sample in less than 2 hours, allowing the rapid selection of the best treatment, improving AMR stewardess, and becoming a significant breakthrough in AMR diagnostics.

Cheeeeeeers

We are veeery happy to announce we have received a 3-year grant from the Spanish Research Agency, to study the molecular determinants of neuronal death in mitochondrial disease. We want to understand the role of the immune system in mitochondrial disease, both in animal models and in human samples, and thanks to this grant we will work to figure it out. We also received a fellowship for a PhD student, so, hopefully, Quintanalab will grow soon 😊

A science dissemination contest was organized at our research institute for Sant Jordi. Laura Sánchez won the first prize with this amazing masterpiece, which shows our lab and the things you can find in it! She rocks!

We have received a Proof of Concept UAB grant to transfer our mito-based technology to develop a diagnostic kit for bacteria resistance. The project, which is a collaboration with Hospital Parc Taulí, will consist of creating a fast and highly sensitive approach to detect antimicrobial resistance (AMR), based on checking the expression of different resistance genes. The development of this disruptive methodology could represent a significant step forward in the fight against AMR, allowing clinicians to find a precise antibiotic for each case 👩‍🔬🦠💪👏

These grants are supported by the Secretaria d’Universitats i Recerca of the Departament d’Empresa i Coneixement de la Generalitat de Catalunya and are funded by the Fons Europeu de Desenvolupament Regional (FEDER).

More info about the project

As the new year begins, we would like to look back to 2020 for a last minute. It was a tough year, but the scientific community got two amazing new doctors!

Pati defended her PhD, ESTUDIO DEL PERFIL TRADUCCIONAL CITOSÓLICO Y MITOCONDRIAL DE POBLACIONES NEURONALES SUSCEPTIBLES A LA DEFICIENCIA DEL COMPLEJO I MITOCONDRIAL, in December, giving an excellent presentation that led to a very interesting discussion.

And Pablo defended his thesis, GLUTAMATERGIC VESTIBULAR NEURONS SUSTAIN MOTION-INDUCED AUTONOMIC AND AVERSIVE RESPONSES, online in July. He did a super-great job as well, it was a great presentation with a very nice discussion. Look at him holding his little baby:

We are veeeery proud of them, and wish all the best for their scientific careers! We already have their pictures on our hall of fame:

We have big good news at Quintanalab.

1. Pati already deposited her PhD
2. Eli was selected to be a Ramon y Cajal researcher
3. Albert is now a tenured associate professor

Everything was adequately celebrated with pizza last Friday:

We are very happy!

Cheeeers!

Albert and Eli participated in an international study published in Nature, which describes the processes occurring in the hippocampal neurons to create long-lasting memories.

Long-term memory is a brain mechanism that allows us to encode and retain an almost unlimited amount of information throughout our lifetime. Key proteins that activate protein synthesis, such as the eIF2 initiation factor, are involved in the process.

In this study, coordinated by McGill University (Montreal, Canada), they observed that eIF2 is involved in the formation of new long duration memories through its activity in two types of neurons in the hippocampus: excitatory neurons and neurons expressing somatostatin, a group of inhibitory neurons.

In parallel and autonomously, the reduction of eIF2 bound to a phosphorus molecule (phosphorylated) in these two subpopulations is enough to increase protein synthesis, strengthen connections between neurons, and improve long-term memory.

“To study these effects, we used a technique we had developed, that showed that the changes in the excitatory neurons during learning are similar to those observed by genetically preventing eIF2a phosphorylation in these neurons”, explains Eli. This is important because it validated the genetic model and allowed identifying the changes that learning produces at a transcriptional level.

“The existence of two autonomous processes for memory consolidation mediated by the non-phosphorylated form of eIF2a may respond to an evolutionary advantage in ensuring and regulating the duration of a given memory”, says Albert.

The study is the first to analyze separately the role of excitatory and inhibitory neurons in the hippocampus in the consolidation of these types of memories, and helps to understand the creation and maintenance of memories phenomenon, which continues to belargely unknown.

Read the article

We are very happy to announce we have been selected to receive a grant from La Caixa Foundation to investigate new therapies for mitochondrial disease! It has been a very competitive process, in which only 8 projects were selected out over 150 proposals, so we have some cava in the fridge!

Our project will focus on studying the alterations that occur in a specific area of ​​the brain, the basal ganglia, in mitochondrial pathologies. We suspect that these alterations are caused by signals initiated in the mitochondria that drive cells to their death. Thanks to the funding from La Caixa Foundation (500,000 euros in 3 years), we will investigate how to reverse these signals and look for new therapies.

Cheeeeers!

What was last Saturday’s day number? Yes, it was the 4th of July. What happens on every 4th of July? Yes, we celebrate a BBQ to commemorate the United States’ Independence Declaration. O say, can you see by the dawn’s early light…  You can tell we miss Seattle 😀

We went to El Bosc Tancat, in Cerdanyola, with our cars full of hot dogs, burgers (+ veggie burgers), chorizo, chicken, omelettes, beers, and a bit of sadness, as it was Fab’s farewell as well.

Marco and Adan were the BBQ chefs, and Fab was in charge of them having enough drinks. They did an excellent job, as the food was de-li-ci-ous. Isabella brought this almost-non-alcoholic potion they drink in Serbia, rakija, to help the food disintegrate in the guts.

After the lunch, we gave Fab some presents, such as a magnific apron he is committed to wear every time he cooks Spanish food:

Then, some dared into the swimmingpool to have an afternoon bath and show how tanned they got during lock-down:

What a pleasure to be part of this group of amazing people! <3