Research challenges theories about our bodies' most important cells

cells Image copyright Heriot-Watt

Researchers at Heriot-Watt university are challenging existing theories about the workings of some of our bodies' most important cells.

They've gained new insights into how cells transport chemicals, the hormone insulin and the brain chemical serotonin, in a project that combined biophysics and mathematics.

It could one day have implications for the treatment of diseases like diabetes and neurological conditions.

Specialised cells in locations like our brain or pancreas create the helpful chemicals and transport them to the surface in tiny bubble-like structures called vesicles.

Deep inside a cell, these vesicles travel along similar chemical tracks towards the surface.

When they arrive at the cell surface, they still move towards certain points but the tracks cannot be seen.

Image caption The university's work has taken seven years of intensive research

The team established why: the tracks are not there. Instead, the vesicles are avoiding other molecules.

It's a breakthrough, but it's not been instantaneous. It has taken seven years of intensive research.

It is that long since Heriot-Watt biophysicist Prof Rory Duncan explained the problem of the missing tracks in a lecture.

Happily, there was a mathematician in the house.

Image copyright Heriot-Watt
Image copyright Heriot-Watt

"This guy from maths, who thinks very, very differently to the rest of us, said it looks these things are following valleys between mountains," Prof Duncan said.

The "guy from maths" was Prof Gabriel Lord. He showed me an animation based on his mathematical model of what happens when the vesicles leave their tracks and move across the surface of the cell

"What we've shown happens is that these vesicles move between the valleys of these other molecules - and they'll do so with some randomness", he says.

What took so long? Gathering a massive amount of data on vesicle behaviour.

That involved using the microscopes of the Edinburgh Super-Resolution Imaging Consortium (ESRIC) based at Heriot-Watt.

Image caption Still images and recordings were made after the cells were viewed under powerful microscopes

It was able to gather nano-scale information of the movements within cells.

To give you an idea of that scale, the vesicles were about as small to us as Jupiter is huge.

Dr Ali Dun manages ESRIC and did her PhD work on the vesicle project.

She said: "I'd get the cells ready, get the DNA together to be able to put into those cells, get the cells onto the microscopes.

"And we have some really amazing microscopes.

"We'd image those cells and get some movies and recordings, take those off, put them onto some very sophisticated software and do the analysis."

Some of the images are things of beauty in their own right.

Image copyright Heriot-Watt
Image caption Thousands of vesicle tracks cover the surface of a cell

One, showing hundreds of thousands of vesicle tracks across the surface of a cell, has more than a touch of Jackson Pollock about it.

Wrangling with the huge amounts of data and building a computer model of how the cells get their precious payloads to where they are needed was where the mathematics came in.

Maths may be the language which underpins all of science but there was still a difference in dialects between the two cultures.

"It was one of the biggest challenges of my PhD," Dr Dun said.

"I've learnt a whole new language working with a mathematician - and I think Gabriel probably feels the same way."

Now the team has published its research in the journal Current Biology, what next?

Prof Duncan warns that it typically takes years to bring new medicines to patients but he says there are implications for new treatments..

"If you have diabetes or certain neurological conditions, for example, something has probably gone wrong with the movement of the cargo in these vesicles inside your cells - and we really don't know what.

"What our new work gives us is a really strong, correct starting point to try to investigate this in the future."

Image caption Prof Gabriel Lord was able to establish that the vesicles move between the "valleys" of other molecules

For Prof Lord, the mathematical modelling approach may lead far beyond biology.

"It's an approach that's going to be used in finance, in astronomy, all over the place."

The work is a prime example of how collaboration between scientific disciplines is amplifying what we can discover.

It was funded through the Next Generation Optical Microscopy Initiative led by the Medical Research Council.

The biologists could use their super-powerful microscopes to see inside the cells to the vesicles. The mathematicians used the data to look closer still.

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