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Hello Brain • Research
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Gene hunt is on

Studying role of novel disease genes in cognition The role of novel disease genes in cognition

Scientists from around Europe are joining in a hunt for genes involved in cognition problems.  We now know genes play a role in cognitive disorders. This includes autism, Alzheimer’s disease, schizophrenia and also dementia.  But it is never as simple as one gene, one condition. 

 “Cognition itself is not the product of one gene in the genome,” says Prof Seth Grant, a neuroscientist at the University of Edinburgh involved in this gene hunt. “Cognitive capacity instead is built up from many different genes. We wish to know what are those genes and what do they do to give us the capacity for reasoning and thinking, learning and memory.”

Mutations in over 400 genes have already been linked to learning, memory and problem-solving difficulties. 

The brain’s tremendous complexity at the level of individual molecules only became clear in the last ten years. The synapses that link nerve cells, for example, were supposed to be relatively simple, but research has shown thousands of proteins play a role in these junctions.  These are critical for learning and memory, so damage to these junctions can cause brain problems.  

Mice and men

The riddle that Grant and his colleagues in the project – called GENCODYS – want to solve is which genes are the master regulators, those managerial molecules that shout instructions and are responsible for building nerve junctions and everything else needed to make what we call cognition. If they go wayward, you have a problem.

To delve into genes and brain disorders the GENCODYS scientists will use mice and flies, two common lab animals used to “model” diseases. “It is possible to create a mouse with the same mutation as a human and then allow it do psychological tests and reward it with food. You can see if it has similar cognitive disorders to a human,” Grant explains. Master regulators are so critical they remain unchanged through millions of years of evolution.

“It is our ambition to take this forward and test some of our proposed drugs in mouse or fly models and see if they rescue or reverse the cognitive impairments in those animals. If such compounds did work we would expect to be in a position to perform clinical trials on humans [to see if we’ve discovered a new drug].”

Fixing what’s broken

The anatomy of the brain has been understood for over a hundred years, but scientists like Grant are now looking in much finer detail at the molecules that go into small, essential brain parts like synapses and even the biological machines inside cells. “There is still a long way to go before we understand cognition. We will need to understand how the many different proteins work together,” says Grant. 

These proteins are the cogs and wheels of biological machines at work within cells; any faults in genes affect how the protein they encode is made. Faulty proteins can leave these important machines within cells broken, damaged or faulty, leaving the cell unable to function properly. This can lead to poor brain function.  Understanding faulty genes – what causes the machines to break – is what gives scientists like Grant ideas about how to fix what is broken using new drugs.

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