Crick scientists receive more than £3million from two Wellcome Trust grants

Crick group leaders have received two separate Wellcome Trust grants, one to study the genes that cause health problems in Down Syndrome, and a second to identify the mechanism behind how ribonucleoproteins and RNA interact and their role in motor neuron disease. 

Spatial memory in people with Down Syndrome

Victor Tybulewicz, group leader at the Crick’s Immune Cell Biology Laboratory & Down Syndrome Laboratory, is a co-recipient of a Wellcome Trust Collaborative Award in Science for £3.8m. The five-year project aims to identify the genes that negatively affect spatial memory in people with Down Syndrome. 

People with Down Syndrome inherit three copies of chromosome 21 instead of two, meaning they have an extra copy of all its genes. They also have high levels of a neurotransmitter which inhibits activity in the area of the brain important for learning and memory. The researchers hope to find the genes on chromosome 21 which are involved in creating this neurotransmitter, called gamma-aminobutyric acid.

“Finding out which of the roughly 230 genes on chromosome 21 are involved in causing health problems when they appear in three copies instead of two is a crucial first step in developing therapies to potentially alleviate adverse symptoms of Down Syndrome,” says Victor.

The collaborative award has been granted to the Down Syndrome Laboratory at the Crick, which received nearly £1m of the grant, while three groups at University College London and one group at Queen Mary University London received the rest of the funds.

Regulating and guiding RNA 

Jernej Ule, group leader of the RNA Networks Laboratory, and Nick Luscombe, group leader of the Bioinformatics and Computational Biology Laboratory, have jointly been awarded a £2.2m Investigator Award in Science for an interdisciplinary project studying complexes called ribonucleoprotein complexes, which are made up of RNA and RNA-binding proteins. These complexes play a crucial role in helping RNA to function correctly, for example they guide RNA to the right location in a cell to carry out a given task.

This collaboration between experts in RNA and specialists in advanced computational methods is a great example of how, by sharing tools, techniques and ideas, we can learn more about important biological molecules
Nick Luscombe

The two Crick laboratories have a long-standing collaboration exploring the structure and function of RNA. Building on previous joint research, the teams will share their expertise in bioinformatics and RNA to determine how the structure of RNA affects the assembly of ribonucleoprotein complexes, as well as establish their roles in the transport and regulation of RNAs in nerve cells in the brain. 

Together, they will also look into what goes wrong with the complexes in motor neuron disease, a fatal progressive condition which affects around one in 50,000 people in the UK and causes problems with movement, eating and breathing. By understanding how the assembly of ribonucleoprotein complexes changes in cases of motor neuron disease, the team hope to identify potential therapeutic targets. 

“This collaboration between experts in RNA and specialists in advanced computational methods is a great example of how, by sharing tools, techniques and ideas, we can learn more about important biological molecules,” says Nick. “For over 10 years, Jernej and I have worked together in this space and, in the Crick, our labs are in the same building for the first time. With this grant, we’ll be able to continue our interdisciplinary research into RNA, how it interacts with other molecules and the implications this has for health and motor neuron disease.”

“With this grant we’re able to build exciting new experimental tools which will help us understand more of the biology behind these vital complexes, and the role they play in disease,” says Jernej.

This is the second Wellcome Trust grant jointly awarded to the Crick’s RNA Networks Laboratory and the Bioinformatics and Computational Biology Laboratory.

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