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Esther farewell

We are very sad! Esther Molina was with us for a few months, but we had to say goodbye to her on Friday. She went back to Valencia, to continue working on “ancient mitochondria”, at Institute for Integrative Systems Biology. It was a great pleasure to have her around!
Marta, our meme artist, prepared this piece for her:

Funding by the Spanish Research Agency

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 😊

Montgat beach

We were at Montgat beach las weekend (enjoying the bad weather!), to celebrate that Fab is around for a few weeks and that Esther (a PhD student at Universitat de València) will be with us for 3 months. It was also Pati’s birthday, so… many things going on!
We played volleyball, gossiped, and ate the worst pulpo a la gallega that Adan (our Galician master student) ever had!
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We have received a Proof of Concept UAB grant!

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

Marie Curie fellowships

 

We have EXCELLENT news: Laura and Marta got both a Marie Curie fellowship!
They are brilliant – this is an extremely competitive grant, especially this year that the European Commission received a record number of applications.There were more than 11,000 proposals, and only 1,630 were selected. Two of them are Laura’s and Marta’s!

The grant will allow them to work for two years on their projects at our lab:
Marta will be working on the MitoTROJAN project, based on the hypothesis that the bacterial origin of mitochondria can trick altered neurons in mitochondrial disease patients into believing they have been infected, which leads to their cell death. She wants to identify the mechanisms involved in this response to identify novel therapeutic targets not just for mitochondrial disease but other pathologies linked to mitochondrial dysfunction, such as neurodegenerative diseases and cancer.
On the other hand, Laura will study cerebellar mitochondrial alterations in Rett Syndrome, a genetic disease in which some genes encoding for mitochondrial proteins appeared differentially expressed. Since the cerebellum is one of the brain regions with higher energy requirements, she wants to study the vulnerability of its different cell types to suffer mitochondrial alterations. The project will provide novel insights into the pathophysiology of this disease, by unveiling potential therapeutical targets.

 

Two amazing new doctors

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:

Our project has been selected by La Marató 2019

Our research project ‘Modulation of mitochondrial retrograde signaling as a treatment for Leigh syndrome’ has been selected by La Marató de TV3 Foundation, within its 2019 edition, dedicated to rare diseases, to receive 300,000 euros of funding.

It is a collaboration between Dr. Francesc Xavier Soriano’s lab and ours, in which we are going to study mitochondrial retrograde signaling (RTM), a mechanism neurons use to compensate for alterations produced by mitochondrial dysfunctions. Potentiating RTM through drugs as CBD is an interesting therapeutical approach for mitochondrial disease, but we still have to better understand how RTM works to find these drugs that can have the best effectiveness.

We are really glad to have this opportunity!

Gooooood news

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!

How is long-term memory created and consolidated?

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

La Caixa Foundation will fund our project!

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!

4th of July

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

Mitowomen

We have been told about this great project, Mitowomen, which is a database to make the women working on mitochondria research more visible. The aim is to create a network for collaboration and to boost women representation on editorial boards, as keynote speakers in conferences, in invited special issues, as reviewers, on grant funding panels or as expert researchers for media consultation or interviews.
As it is such a great initiative, we wanted to share it with you! Check their website out and follow them on Twitter.

NEW ARTICLE!

Emma is the first author of an article published in Nature Communications about the existing differences among neurons expressing dopamine D2 receptors in the striatum. It is an international collaboration in which Albert and Eli also participated.

The striatum is a brain region involved in motor control, habit formation, decision-making, motivation and reinforcement, among other aspects, and its disfunction has been associated with many neurological and psychiatric disorders. One of the most important neurotransmitters in the striatum is dopamine, which exerts different functions depending on the kind of receptor it binds to.

This study, which is an international collaboration, focused on D2 receptors, and showed that, contrary to paradigm, not all D2 neurons within the striatum have the same molecular identify or function, but that their neuro-anatomical localization is key.

Using cutting-edge technologies, they analyzed mouse models to see what genes are expressed in D2 neurons from the two main areas of the striatum: the ventral striatum, consisting mainly of the nucleus accumbens, and the dorsal striatum, and revealed overwhelming differences among them. Thus, depending on their precise anatomical location, they express different kinds of proteins, changing neurons’ features and functions.

They also focused on a group of neurons mainly located in the accumbens, which express the protein WFS1, and studied the effects of deleting their D2 receptors. What they observed was a significant reduction in digging, an innate behavior used in many species to seek or hoard food, as shelter, or to hide away from predators, whose underlying neuronal mechanisms were still unknown. Additionally, the authors found that these animals present an exacerbated hyperlocomotor response when their dopamine levels are increased through amphetamine administration, suggesting a key role of D2 receptors from WFS1 neurons in the response to psychostimulants.

Overall, this study demonstrates that there is a huge complexity and functional specificity among D2 neuron subpopulations, and reveals the possibility to manipulate them specifically to better understand their functions, in both physiological and pathological contexts.

We try to stay safe and help as much as we can!

These are difficult days all around the world. Here in Barcelona, the number of infected people is still increasing, with no prospects for improvement in the short term. Hospitals are facing a lack of human and material resources, hence our University made a call to gather protection and detection equipment. Among other material, they collected around 90000 gloves and 4000 masks. Great job!

In the Quintana lab we are trying to help as much as we can, donating protection equipment and loaning an extraction station to Parc Taulí Hospital. This machine is an automatic processor for obtaining nucleic acids, that can be used for the diagnose of CO-VID19.  Also, some people in the lab offered their hands to help doing PCR diagnosis if the Health Department needed it.

We stay at home, but try our best to continue with the scientific activity. Today we did our first long distance lab meeting, pyjamas allowed:

We hope everything will get better soon, and all of you will be okay!

Take care <3

Celebrating Thanksgiving

Weren’t you missing a post about Thanksgiving? We celebrated it, OF COURSE! Almost all of us gathered together in Albert and Eli’s house, to eat delicious food and drink delicious wine. The hosts prepared the main dish: a huge turkey (14-pounder) that went into the oven at 10 in the morning so it could be ready at a reasonable time (unlike other years). Guests brought other tasty side dishes, such as cornbread or amazing cakes. Big applause for everyone, as everything was excellent!

With some extra kilos (or should I say pounds?), we then played a game Alex brought, called Timeline, in which you have to put in order historical events. Guess who won? Albert, of course. And also Mel, who was playing with the youth handicap.

It was a lovely day with the best company!

The VII INc Scientific Conferences

At the beginning of the month, the Institut de Neurociències celebrated its 7th Scientific Conferences, and we were -obviously- there!

The event was held in Sant Feliu de Guíxols, by the sea, in the nicest hotel, and gathered together more than 120 students and institute members.

Albert was the conference coordinator and worked very hard for everything to be perfect.

There were more than 30 talks, poster sessions and time for having fun, as well:

(Please, take your time to observe this picture of the costume contest, don’t miss any details…)

Several members of the group participated in the conferences: Elisenda gave a talk on the first day regarding new techniques we are using, Patrizia explained the research she is currently carrying out, and Emma chaired a scientific session. Also, Andrea, Laura, Pablo, Pati and Patrizia presented a poster.

On the fun side, Abel organized an amazing trivia game, on the first night, that Laura’s team won. Pablo’s team won the costume contest, dressing as Disney characters; and Albert and Eli won the partying contest, almost closing the disco.

They were great days with great people! Already looking forward next year’s edition!

We received a CaixaImpulse grant

We are very glad to announce that our MitoCBD project has been selected for a CaixaImpulse grant.

MitoCBD consists in investigating the use of Cannabidiol (CBD), a substance obtained from the cannabis plant, for the treatment of mitochondrial disease.

It has been proved that CBD has anti-inflammatory and neuroprotective properties, and it was also found to restore deficits and prolong life expectancy in a mitochondrial disease model.

The aim of this project is to test the effectiveness of the CBD in other preclinical models of mitochondrial disease, with the final objective of finding a treatment for these devastating rare diseases.

There has only been 21 projects selected from all around the UE, so we are veeeery happy that MitoCBD is one of them!

 

New article!

We have a new article! Elife published our study in Leigh Syndrome, the most common mitochondrial disease with affectation of the central nervous System. In this disease, there are two brain regions that are particularly compromised: the brainstem (that controls all basic functions that keep us alive) and the basal ganglia, involved in refining motor coordination. In our study, we wanted to explore the role the protein Ndufs4 has in this affectation.

Ndufs4 is a subunit of the Complex I. It is located in the mitochondrial membrane and is involved in the respiratory chain. We knew that animal models lacking this subunit in all their cells reproduce the classical signs of Leigh Syndrome, but do symptoms appear due to all cells in the body not working properly, or some specific cells are responsible for them?

To study this, we selectively inactivate the gene codifying the protein Ndufs4 in three neuronal populations we suspected could be key, and keep it working in all other cells in the body. Observing what symptoms remained we could know the role of these neurons in the alterations these patients suffer.

What we found was that the inactivation of this subunit in a certain kind of excitatory neurons (the fancy-scientist name is vlgut2-expression glutamatergic neurons) caused brainstem inflammation, motor and respiratory deficits, and early death; and that its inactivation in inhibitory (GABAergic neurons) led to basal ganglia inflammation, severe refractory epileptic seizures and premature death.

These results are very important to contribute understand the underlying cellular mechanisms of Leigh Syndrome, as we identified which specific neurons are behind the brain alterations. Therefore, now we have new knowledge to try to identify which cellular aspects are failing in those cells so we can start to envisage different methods to correct them.

Congrats to all the team and collaborators!

Celebrating the 4th of July

Albert, Eli, Álex and Irene are a bit nostalgic of their lives in USA, and they celebrate every North-American festivity they can.

This time, we met at Andrea’s house in el Penedès (thank you again for offering the house) to honour the USA independence on the 4th of July.

Cold beers in the swimming pool, to fight the heat, and all this tasty food waiting to be cooked in the barbecue.

The burgers needed to be prepared. We mixed the meat while Albert and Eli were singing the US National Anthem. We also had frankfurts and pulled pork, which was extremely delicious.


After the meal, we made up a game with water balloons in the swimming-pool, and we played Dixit while Fabien was putting great music. Abel won not because he was the best but because we used his weird point-counting system.

It was a lovely day! It is great to be part of the Quintanalab 🙂

MitoTreat won the 9th edition of the Generació d’Idees Program!

Generació d’Idees is a program organized by Parc de Recerca UAB, to promote entrepreneurship among researchers. Communications, mental health, environment… They focus on a different topic in each edition, and this time, it was the turn of biotechnology.

During 17 sessions, researchers were given the tools to develop innovative solutions in the biotechnology field. They had modelling classes, mentoring sessions, etc., and then, after all this time, they presented six different projects to a board of experts. The most innovative one was selected… and guess which one was it! Yessss: MitoTreat!

MitoTreat was developed by Emma, Elisenda and Albert, and consists in using Cannabidiol, a substance found in cannabis, to treat mitochondrial disease. Cannabidiol has anti-inflammatory, anti-oxidant, analgesic, neuroprotective and anti-convulsive proprieties.

In animal models of mitochondrial diseases it showed excellent results, and now they want to start the preclinical trial in humans.

The project obtained a 1500 euro prize and 6 months of incubation at Eureka building, at Parc de Recerca, to improve the transference of the drug to the market.

Congrats!

Quintanalab-Calçotada 2019

The Quintanalab-Calçotada 2019 took place on a super sunny April day in El Priorat de Banyeres, a tiny village near Vilafranca. Thanks, Andrea, for offering the house!

It is already a tradition that the whole group gathers together one day to eat calçots with salsa romesco and have fun.

(Please, note Albert’s Salt Bae position…)

Àlex was the calçots chef. A fire was made, and he cooked the calçots with patience and expertise. He did an excellent job as they were very delicious!

After the heavy lunch, to digest, we played dodgeball. Ask Albert who won. Spoiler: not his team.

Then we drunk mojitos and talked and drunk more mojitos… It was a very nice day! Can’t wait for the Quintanalab-Calçotada 2020!

Swiss Light-sheet Microscopy Workshop

Last 24th and 25th of April, Andrea, Pablo, Elisenda and Albert went to Zurich to attend the Swiss Light-sheet Microscopy Workshop.

 

 

It was a two days meeting in which researchers from all over the world gathered together to share the observational techniques they are using. Users and developers discussed newest advances in the field and exchanged ideas.

Elisenda was telling me about these 3D glasses that transported you inside a gigantic transparent brain in which you could observe a specific neuron from all possible angles. Exciting!  Pablo is there in the picture:

 

 

They were very impressed by everything they saw, and learned a lot! Albert said it was a very productive conference and can’t wait to have the chance to try some of these techniques in the lab. He also told me they were happy they had the chance to have a typical Swiss dinner: fondue, raclette and rösti. Fabien might not agree about this being a typical Swiss dinner and not a French one…

Our first preprint!

We published our first preprint last week. For those who aren’t familiarized, a preprint is a study to be published in a Journal, that has not been reviewed yet. The aim is to make the results available as soon as possible so Science can advance faster. We are very excited about it, and very happy because it has been featured by the preprint platform Biorxiv for reaching the top 5% altmetric score within their first days after releasing it; and it has also been selected as one of the ERC Research results of the week! So cool!

But what is it about?

As you may know, dysfunctions of the mitochondrial energy-generating machinery cause a series of usually fatal diseases collectively known as mitochondrial disease. In this disease, high energy-requiring organs, like the brain, are especially affected, showing many severe symptoms such as motor alterations, respiratory deficits or epilepsy that, in many cases, can be fatal. Hence, our group is driven to better understand these pathologies, with the overarching goal of finding effective therapies to treat them.

This time, we focused on Leigh Syndrome, the most common presentation of mitochondrial disease with a predominant affectation of the central nervous system, particularly in two brain areas, the brainstem (that controls all basic functions that keep us alive) and the basal ganglia, involved in refining motor coordination. We knew that one protein in the mitochondria is critical in this disease: the Complex I subunit NDUFS4, because animal models lacking this subunit in all their cells reproduce the classical signs of Leigh Syndrome described before. However, there were some pressing questions remaining: do symptoms appear due to all cells in the body not working properly, or some specific cells are responsible for them?

To study this, we selectively inactivate NDUFS4 in three neuronal populations we suspected could be key, and keep NDUFS4 working in all other cells in the body. Observing what symptoms remained we could know the role of these neurons in the brain alterations these patients suffer.

What we found was that the inactivation of this subunit in a certain kind of excitatory neurons (the fancy-scientist name is vlgut2-expression glutamatergic neurons) caused brainstem inflammation, motor and respiratory deficits, and early death; and that its inactivation in inhibitory (GABAergic neurons) led to basal ganglia inflammation, severe refractory epileptic seizures and premature death.

Bottom line, these results are very important to contribute understand the underlying cellular mechanisms of mitochondrial disease in general, and Leigh Syndrome in particular, as we have identified which specific neurons are behind the brain lesions observed in this pathology and their specific contribution to the symptoms. Therefore, now we have new knowledge to try to identify which cellular aspects are failing in those cells so we can start to envisage different methods to correct them.