MRI tracking of genes to offer insights into memory and learning

Date: Mar-28-2014Doctors normally use MRI to look inside the body to examine organs and tissue, for

instance to find tumors and other abnormalities. Now, biological engineers in the US want to

adapt the scanning technology to work on a much smaller scale.

They want to use magnetic resonance imaging (MRI) as a

"molecular imaging" tool to see genes at work in living brains and find out what effect they

have on cognitive processes like memory and learning.

The team working on this is at Massachusetts Institute of Technology (MIT). Their leader,

Alan Jasanoff, an associate professor of biological engineering, says:

"The dream of molecular imaging is to provide information about the biology of intact

organisms, at the molecule level. The goal is to not have to chop up the brain, but instead to

actually see things that are happening inside."

MRI uses magnetic fields and radio waves to interact with

protons in the body. This interaction produces detailed images of the insides of the body.

Functional MRI allows neuroscientists to see which parts of the brain are active during

various tasks by "seeing" where the blood flows. When scanning other organs, doctors sometimes

use magnetic "contrast agents" so the tissue they are investigating stands out more clearly.

What the MIT team has done is develop an artificial "reporter gene" that switches on and off

to signal certain events in the body - rather like the indicator light that flashes on the

dashboard of a car.

New MRI to track reporter gene at the molecular level

The idea is to image the reporter gene with MRI technology at the molecular level.

In a study reported in the journal Chemical Biology, the researchers describe how

the reporter gene encodes an enzyme that interacts with a magnetic contrast agent injected into

the brain. So when the gene is switched on, it produces the enzyme, which interacts with the

contrast agent in such a way that MRI can see it, and thus the researchers can track

where and when the gene is switched on in the brain.

In the case of this particular study, the team used a contrast agent called manganese

porphyrin. And the reporter gene they developed codes for a genetically engineered enzyme called

SEAP that changes the electric charge on the contrast agent.

The MIT team devised the contrast agent so it could be soluble in water and readily

eliminated from the body. On its own, it is difficult to track with MRI, but when it

encounters SEAP, the enzyme slices phosphate molecules from the manganese porphyrin, which

causes it to become insoluble. The agent gradually builds up in brain tissue and becomes

visible with MRI.

Researchers plan to investigate 'early immediate genes' in brain

plasticity

The purpose of this study was to show that the SEAP gene could be successfully incorporated

into brain cells.

In future studies, the team hopes to engineer the SEAP gene so it is only active - and thus

making the enzyme - when a particular gene that the researchers want to study is switched

on.

The first genes they want to investigate with this method will be what the team calls "early

immediate genes," which are important for brain plasticity - the strengthening and weakening of

links between neurons, which forms the basis of learning and memory.

Prof. Jasanoff, who is also an associate member of MIT's McGovern Institute for Brain

Research, says:

"As people who are interested in brain function, the top questions we want to address are

about how brain function changes patterns of gene expression in the brain."

Assaf Gilad, an assistant professor of radiology at Johns Hopkins University who was not

involved in the study, says:

"These kinds of genetically engineered reporters have the potential to revolutionize our

understanding of many biological processes."

The Raymond and Beverly Sackler Foundation, the National Institutes of Health, and an MIT-Germany Seed Fund grant helped finance the study.

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Written by Catharine Paddock PhD




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