Spotlight: The Neuro-D lab Leiden

Principal Investigator: Dr. Willeke van Roon-Mom

Location: Leiden University Medical Centre, Leiden, The Netherlands

Year Founded: 1995

What disease areas do you research?

What models and techniques do you use?

A group photo of members of the Neuro-D lab Leiden standing outside on a patio.
This is a group picture taken during our brainstorm day last June. From left to right: Boyd Kenkhuis, Elena Daoutsali, Tom Metz, Ronald Buijsen, Willeke van Roon-Mom (PI), David Parfitt, Hannah Bakels, Barry Pepers, Linda van der Graaf and Elsa Kuijper. Image courtesy of Ronald Buijsen.

Research Focus

What is your research about?

The Neuro-D research group studies how diseases develop and progress at the molecular level in several neurodegenerative diseases. They focus on diseases that have protein aggregation, where the disease proteins clump up into bundles in the brain and don’t work correctly.

We focus strongly on translational research, meaning we try to bridge the gap between research happening in the laboratory to what is happening in medical clinics. To do this we use more “traditional” research models like animal and cell models. But we also use donated patient tissues and induced pluripotent stem cell (iPSC) models, which is closer to what is seen in medical clinics.

Our aim is to unravel what is going wrong in these diseases, then discover and test potential novel drug targets and therapies.

One thing we are doing to work towards this goal is identifying biomarkers to measure how diseases progress over time. To do this, we use sequencing technology and other techniques to look at new and past data from patients.

Why do you do this research?

So far there are no therapies to stop the progression of ataxia. If we can understand what is happening in diseases in individual cells, we can develop therapies that can halt or maybe even reverse disease progression.

Identifying biomarkers is also important, because it will help us figure out the best time to treat patients when we eventually have a therapy to test.

Stylized logo for the Dutch Center for RNA Therapeutics
The Neuro-D lab Leiden is part of the Dutch Center for RNA Therapeutics, which focuses on RNA therapies like antisense oligonucleotides. Logo designed by Justus Kuijer (VormMorgen), as 29 year old patient with Duchenne muscular dystrophy.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for a SCA1 natural history study and biomarker study. More information can be found here. Please note that information about this study is only available in Dutch.

Fun Fact

All our fridges and freezers have funny names like walrus, seal, snow grouse and snowflake.

For More Information, check out the Neuro-D lab Leiden website!


Written by Dr. Ronald Buijsen, Edited by Celeste Suart

Spotlight: The Watt Lab

Watt lab logo of a neuron

Principal Investigator: Dr. Alanna Watt

Location: McGill University, Montreal, Canada

Year Founded: 2011

What disease areas do you research?

What models and techniques do you use?

Research Focus

What is your research about?

We are interested in how the cerebellum influences motor coordination in both the healthy brain and in models of disease and aging. By identifying changes in the cerebellum underlying ataxias and aging, we hope to discover new treatments for patients.

Why do you do this research?

We want to understand how the cerebellum works and use this knowledge to understand the changes in the cerebellum that lead to ataxia. As a lab, we are particularly interested in studying rare disorders like SCA6 and ARSACS.

These disorders have limited treatment options. We hope that by understanding how the cerebellum works differently in these disorders, we will be able to identify new treatments to help ataxia patients.

We are also interested in identifying common changes between different types of ataxia, to find out whether treatments identified in one form of ataxia might also help other ataxia patients.

Six slippers with a variety of designs, includes brain cells and mice

Fun Lab Fact

We got together and made our own slippers to keep cozy in our office. If you look at the picture closely you might be able to spot some cells from the cerebellum on some of them!

Image courtesy of Anna Cook.

For More Information, check out the Watt Lab Website!


Written by The Watt Lab, Edited by Celeste Suart

Snapshot: What is RNA-seq?

RNA-seq is a technology that has been used more and more in recent years to study both basic biology and disease. It’s a powerful tool has enabled scientific discovery at an unprecedented rate. But what exactly is RNA-seq? And, more importantly, what can it tell us?

RNA-seq is short for “RNA sequencing.” In essence, it’s quite similar to a technique you may have heard of before: whole genome sequencing. Our genome (i.e., our genetic code) is made up of DNA, which consists of 4 building blocks – chemicals abbreviated as A, T, C, and G – that are strung together in a code. Just like how different sequences of letters in the alphabet make up different words and sentences, different sequences of DNA building blocks make up the many different genes in our genome.

In whole genome sequencing, researchers determine the DNA code for every gene in an organism’s body. RNA sequencing, on the other hand, provides the sequence of a related chemical code: RNA.

What is RNA?

Picture a library full of shelves upon shelves of books. Together, the books contain all the instructions to make every piece of our bodies – everything from the smallest molecule in a cell to a whole organ. In this example, the books are our genes, and every cell in our body contains the whole library.

a densely densely back library shelf with an assortment of books
A library full of shelves of books, much like a human cell full of DNA. Photo by Alfons Morales on Unsplash.

Say a cell needs to make protein X . Instead of checking out the book, a copy of the book is made. That copy is called RNA, which will then be used to make protein X. This copy-making process, known as “transcription,” gives the cell more flexibility when it comes to how much of protein X to produce: in general, the more protein X the cell needs, the more copies of RNA are made. The total amount of protein X that is made from its gene is called “gene expression.”

What can we learn from RNA?

Because each of our cells has a specific role, they do not express every one of our genes; like us, they only read the books that are relevant to the topic at hand. If a gene is not expressed, even when we have it on the shelf, it is not functional. So, if we could have a readout of what genes are being expressed in a certain tissue, we could better understand what the cells in that tissue are doing. The easiest way to do that is by sequencing RNA.

How can we use RNA-seq for research?

One of the great things about RNA-seq is that it provides information about not only which genes are being expressed, but how much each gene is being expressed. For instance, as we age, the amount of growth factor produced by our body drops. If you perform RNA-seq on tissue samples from both a child and an adult, you can expect increased gene expression of growth factors in the child (indicated by an increased amount of growth factor RNA in the child’s tissue sample).

Gene expression is affected by a number of other factors, as well. In the case of illness – even when the disease is caused by a mutation in a single gene – a number of genes are likely to be differentially expressed as the result of your body’s attempt to compensate. If we compare an ataxic patient to a healthy individual, for example, we can expect to find hundreds of differentially expressed genes.

By comparing healthy individuals and patients using RNA-seq, we can learn what gene expression patterns are altered in disease. Tapping into this information helps scientists determine what went wrong in a specific disorder, which then informs them about what to do next. Whether this leads them to identify biomarkers, honing diagnostic strategies, or developing new treatments, RNA-seq acts as an important preliminary step in their research.

To learn more about the process of gene expression, check out this animation.

If you would like to learn more about RNA-seq, take a look at these resources by Thermo Fischer Scientific and Bite Size Bio.

Snapshot written by Sophia Leung and edited by Maxime Rousseaux.

Snapshot: What is RNA?

RNA is an important molecule that helps with regulating the function of cells. To fully understand how RNA fits in here, we must first look at the bigger picture: genetics. The central dogma of molecular biology, depicted below, states that DNA is copied (transcribed) into RNA, which is later decoded (translated) into proteins, which perform many vital functions in the cell. So, when the cell needs a specific protein, it locates the stretch of DNA that contains the code for this protein and starts to write a copy of that stretch of DNA. This copy is made using RNA, or ribonucleic acid, as a backbone. RNA is very similar to DNA, but contains one extra oxygen atom in the basic building block. Only one strand of the DNA is copied, so RNA ends up looking like half a DNA molecule. The RNA molecule can be seen as the messenger between the archive of your genes (DNA) and the protein production site. However, RNA is very versatile and is also involved in protein regulation, transport of molecules and as a structural component of large complexes in the cell.

The "central dogma" of molecular biology: DNA makes RNA, then RNA makes protein.
The “central dogma” of molecular biology: DNA makes RNA, then RNA makes protein. Adapted from Wikimedia.

The shifting stream of RNA

Apart from small random mutations during the course of a lifetime, the DNA contained in every cell remains the same from birth to death. However, since different cells need different proteins at different stages of growth, there needs to be a selection of which genes are copied and translated into proteins. This means that the process of making RNA has to be very flexible. This flexibility is achieved through a large network of signals that tell the cell which regions of DNA should be transcribed into RNA, and at what rate. To keep up with the demands of the cell, there are millions of RNAs being made at all times, to send out instructions to makes proteins.

How can RNA cause disease?

In some spinocerebellar ataxias, such as e.g. SCA8, the messenger RNA molecules contain long repetitive sequences that become sticky to other copies of the same RNA or to proteins, forming both small and large clumps in the cell. There is still controversy surrounding which steps in the process that ultimately causes cell death in large brain areas, but it seems that unsolicited binding of these sticky RNAs to proteins and other RNAs causes disruption to several functions in the cell simultaneously. Therefore, many researchers are hopeful that reducing the amount of these RNAs in the cell using Antisense Oligonucleotides or RNA interference can help treat spinocerebellar ataxias and other similar diseases.

If you would like to learn more about RNA, take a look at these resources by the Encyclopedia Britannica and Khan Academy.

Snapshot written by Frida Niss and edited by Dr. Hayley McLoughlin.