Carol Robinson: Pushing a technology’s boundaries

The distinguished chemist Carol Robinson has used mass spectrometry
throughout her career to tackle increasingly complex problems in
biology. When she delivered the Radcliffe Institute’s first Lecture in the Sciences
of the academic year, last Oct. 6, she chose the title “Reading
Between the Spectral Lines,” referring to the jagged lines of data
produced by the mass spectrometer.

This technology allows scientists to
analyze the chemical structure of a sample by determining the precise
mass (or size) and charge of particles in it. 

Robinson’s
career has followed a non-traditional path, but it has always been
propelled by a desire to find new ways to use mass spectrometry to
understand molecules in cells. Now a professor of biological chemistry
at the University of Cambridge, she left school as a teenager and began
working as a technician in the pharmaceutical industry in 1960, when
mass spectrometers were large machines “with lots of dials and meters
to look at” that she instantly loved.

At the time, these machines were
used to analyze small molecules such as drugs. The molecules were
fragmented into particles and passed through an electromagnetic field,
which caused the fragments to produce unique signatures based on their
mass and charge. Growing bored with work in industry, Robinson earned
her college degree and later left her job to pursue a master’s and a
doctorate at the University of Cambridge. By this time, mass
spectrometers had advanced to the point where they could handle larger
molecules, including very small proteins.

Robinson then took an eight-year career break to raise her children.
During that time, she said, a major development transformed mass
spectrometry into a crucial technology in modern biology. This new
technique allowed scientists to analyze large molecules such as entire
proteins. The ability to use mass spectrometry to identify and analyze
proteins — the main chemical actors in cells — gave rise to the field of
proteomics, or the study of all proteins in the living cells.

Robinson returned to science and began to further push the boundaries
of mass spectrometry. She demonstrated that it could be used to
understand the structure and arrangement of molecules, not just to
identify their constituent parts. For instance, proteins fold into
three-dimensional structures that are critical for how they interact
with one another and with parts of the cells.

Robinson said she set out
“to use mass spectrometry to monitor the process of folding.” In one
case, she and her colleagues developed a method of labeling parts of
proteins so that changes that occurred during folding could be detected
in a mass spectrometer.

Although capturing the structure of a protein is important, many
proteins work in complexes with other proteins or other molecules in
the cell. More recently, Robinson’s lab has been using mass
spectrometry to analyze the structures of large protein complexes,
something that few would ever have thought could be accomplished with
mass spectrometry.

Her team has shown that these complexes can be
treated gently enough that researchers can identify the essential
building blocks of a complex and then match that data to mathematical
models to explain how the blocks might be arranged. Robinson said,
“It’s sort of like solving a jigsaw puzzle.”

Courtney Humphries is a freelance science writer. This article first appeared in the Radcliffe Quarterly.