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.

The wheels are running!

Wow! what a busy time this past year has been!

Many (good) things and (good) news to explain! New members, new papers, exciting science… here you are a picture of the lab just before summer break!

quintanalab 2017

First of all, we are glad to announce three! new additions to the lab: Kelsey, Fabien and Patrizia. (disclaimer: they have already been with us for some months, but hey, I told you we have been really busy!)

Kelsey Montgomery has re-joined the lab as a part-time research technician/MSc student (Bioinformatics). She graduated (BSc. Genetics) from the University of Georgia (2013) and worked at Seattle Genetics (2013-2015) before joining the Quintana lab in Seattle (2015). We are excited to have her with us again on the other side of the pond!

Fabien Menardy (aka Fab) has joined the lab as a postdoctoral fellow and is our resident optogenetics/in vivo electrophysiology expert. Fabien graduated (PhD Neurosciences) from the University of Paris Sud (2012) under the supervision of Dr. Catherine del Negro, where he worked on elucidating neural responses involved in zebra finch vocal communication signaling. After obtaining his PhD, he joined the lab of Dr. Daniela Popa and Dr. Clément Lena, at the École Normal Supérieure, Institut de Biologie (Paris), as a postdoctoral researcher (2013-2016) where he focused on understanding the role of the cerebellum in Parkinson’s Disease. He is now interested in understanding the electrophysiological alterations (and their implications in circuit signal processing) in neurons with mitochondrial dysfunction. 

Patrizia Bianchi joined the lab as a postdoctoral fellow and is an expert in mitochondrial dynamics. Patrizia graduated (PhD Biomedicine) from the Universitat de Barcelona (2016) under the supervision of Dr. Aurora Pujol (IDIBELL), where she worked on elucidated the alterations in mitochondrial dynamics in X-linked adrenoleukodystrophy. She is now focusing on characterizing the underlying deficits in mitochondrial dynamics in animal models of Leigh Syndrome.

We are glad to have such talented scientists in the lab!

Last, but not least, and even though there will be other posts providing brief summaries, we are glad to have had two articles recently accepted! Hooray!

Here you are the links, for those interested:

Striatal GPR88 modulates foraging efficiency (Journal of Neuroscience)

Loss of mitochondrial Ndufs4 in striatal medium spiny neurons mediates progressive motor impairment in a mouse model of Leigh Syndrome (Frontiers in Molecular Neuroscience). OPEN ACCESS

Will keep you updated!!