At TCD, Viewing protein folding helps scientists home in on neurodegenerative disease

A team of international researchers led by Professor in Physics at Trinity, Martin Hegner, an Investigator in CRANN, has for the first time observed how proteins fold while being produced in real time.

The work has significant implications for understanding protein synthesis generally, and particularly in neurogenerative diseases such as Alzheimer’s and Parkinson’s. The team’s findings have just been published in the prestigious journal Proceedings of the National Academy of Sciences. The article can be read here.

Professor Hegner’s work focuses on individual ribosomes, which are complex molecules that use genetic information to assemble proteins. There can be several million ribosomes in a typical human cell and they are about 20 nanometres in diameter. The assembly of proteins is crucial for a healthy functioning body as all the proteins in our bodies must fold into complex shapes to do their job.

While protein synthesis is of fundamental importance in cellular processes, how they are created is not fully understood. One of the events that occurs during protein synthesis is “folding”, where the chains of amino acids (polypeptides) fold into their final 3-dimensional structures.

Single ribosome assay.
Single ribosome assay.

Several neurodegenerative diseases (such as Alzheimer’s) and many allergies are believed to result from misfolded proteins. This research is thus important in developing further understanding of such conditions and in developing drugs that can target and prevent certain foldings. There has been interest expressed in Professor Hegner’s work by pharmaceutical companies.

Professor Hegner said: “The ribosome translation machinery is a highly complex system, involving many different factors such as energy input, messenger RNA decoding, amino acids, as well as their relative movements and interactions. Investigating this system at the single-molecule level required a highly ambitious and multi-faceted approach that pushes the boundaries of what is technically possible.

“We have identified key mechanisms within individual ribosomes using our unique optical tweezer instrumentation, of which there are only approximately five world-wide. Our expertise in the design of the device and the biological experiment, along with colleagues in Germany enabled us to “grab” the ribosome and the nascent protein chain and provided sufficient stability and sensitivity to observe the synthesis and folding of single polypeptides in real time at the nanometer scale. This was the first time this was observed world-wide and it is very significant to the research community and in developing more in-depth understandings of protein synthesis, – folding and certain diseases.

Professor Hegner was awarded a Science Foundation Ireland Principal Investigator award in 2016, valued at €1.3m, which will enable him to continue his work in this field.

The structure of the ribosome at atomic resolution was only determined in 2000, for which the Nobel Prize in Chemistry was awarded in 2009.

TCD Physicists Discover a New Form of Light

Physicists from Trinity College Dublin’s School of Physics and the CRANN Institute, Trinity College, have discovered a new form of light, which will impact our understanding of the fundamental nature of light.

One of the measurable characteristics of a beam of light is known as angular momentum. Until now, it was thought that in all forms of light the angular momentum would be a multiple of Planck’s constant (the physical constant that sets the scale of quantum effects).

Now, recent PhD graduate Kyle Ballantine and Professor Paul Eastham, both from Trinity College Dublin’s School of Physics, along with Professor John Donegan from CRANN, have demonstrated a new form of light where the angular momentum of each photon (a particle of visible light) takes only half of this value. This difference, though small, is profound. These results were recently published in the online journal Science Advances.

Commenting on their work, Assistant Professor Paul Eastham said: “We’re interested in finding out how we can change the way light behaves, and how that could be useful. What I think is so exciting about this result is that even this fundamental property of light, that physicists have always thought was fixed, can be changed.”

Professor John Donegan said: “My research focuses on nanophotonics, which is the study of the behaviour of light on the nanometer scale. A beam of light is characterised by its colour or wavelength and a less familiar quantity known as angular momentum. Angular momentum measures how much something is rotating. For a beam of light, although travelling in a straight line it can also be rotating around its own axis. So when light from the mirror hits your eye in the morning, every photon twists your eye a little, one way or another.”

“Our discovery will have real impacts for the study of light waves in areas such as secure optical communications.”

Professor Stefano Sanvito, Director of CRANN, said: “The topic of light has always been one of interest to physicists, while also being documented as one of the areas of physics that is best understood. This discovery is a breakthrough for the world of physics and science alike. I am delighted to once again see CRANN and Physics in Trinity producing fundamental scientific research that challenges our understanding of light.”

To make this discovery, the team involved used an effect discovered in the same institution almost 200 years before. In the 1830s, mathematician William Rowan Hamilton and physicist Humphrey Lloyd found that, upon passing through certain crystals, a ray of light became a hollow cylinder. The team used this phenomenon to generate beams of light with a screw-like structure.

Analysing these beams within the theory of quantum mechanics they predicted that the angular momentum of the photon would be half-integer, and devised an experiment to test their prediction. Using a specially constructed device they were able to measure the flow of angular momentum in a beam of light. They were also able, for the first time, to measure the variations in this flow caused by quantum effects. The experiments revealed a tiny shift, one-half of Planck’s constant, in the angular momentum of each photon.

Theoretical physicists since the 1980s have speculated how quantum mechanics works for particles that are free to move in only two of the three dimensions of space. They discovered that this would enable strange new possibilities, including particles whose quantum numbers were fractions of those expected. This work shows, for the first time, that these speculations can be realised with light.

The journal article can be viewed here.