The latest Business updates from the science industry


by Heather Hobbs Diamond Invests in Physical Sciences Development


Renowned scientist Dr Adrian Mancuso, a well-known fi gure in the light sources’ community has joined the UK’s national synchrotron, Diamond Light Source, as the new Physical Science Director with responsibility for the overall strategic leadership and management of the division.


Adrian joined Diamond from the European XFEL facility, the world’s largest X-ray laser located in Hamburg, where he was Group Leader and Leading Scientist for the Single Particles, Clusters, and Biomolecules & Serial Femtosecond Crystallography (SPB/SFX) instrument Group since 2010.


Professor Sir Adrian Smith, Chairman of the Board of Directors says; “We are delighted to have Adrian join our team with the wealth of experience he brings to the organisation. He not only has extensive scientifi c leadership, but also hands-on knowledge of the pressure to deliver complex experiments for users. As a physicist, his input into the Diamond Executive will be key and his strong interest in technology development and science strategy will be invaluable moving into the detailed planning for Diamond-II.”


Adrian already has a strong connection with Diamond, having served as a member of its Scientifi c Advisory Committee (SAC) for over three years, contributing along with other members of science facilities worldwide to inform on the technical and scientifi c questions impacting the specifi cation, design, commissioning and operation of Diamond. He also holds an adjunct Professorship in the Department of Mathematical and Physical Sciences at La Trobe University, Australia.


Commenting on his new role, Adrian told International Labmate


that the brighter light of Diamond-II will offer the physical sciences community in both academia and industry new avenues of research into the structure of everything from batteries to energy technologies, to new materials.


“I’m delighted to be joining such a broad and successful facility as Diamond. I’m very much looking forward to seeing up close, Diamond’s part in the UK and international scientifi c landscape and being part of discovering even more applications and relationships that will make the most of Diamond’s superlative capabilities to perform societally relevant and fundamental science.


“Diamond-II is the next great opportunity to provide even brighter X-rays for experiments. It leans towards my own experience of using ultra-bright X-rays from X-ray Free Electron Lasers (XFELs) to perform unique investigations into not only the structure of physical and biological systems and more, but also the dynamics of how these materials change in time. Watching what are essentially movies of fundamental processes provides much more insight into how things work—much like the difference between watching a football match or just knowing the full-time score. Diamond, and in future Diamond-II, has both the capability and capacity to be a central contributor to a broad range of science, and I couldn’t be more excited to be part of these next steps.”


Prior to joining EuXFEL, Adrian undertook post-doctoral positions at the University of California (Department of Physics and Astronomy) and the Deutsches Elektronen-Synchrotron DESY, having achieved


Dr Adrian Mancuso


his PhD in Physics from the University of Melbourne in Australia. His areas of expertise include imaging using spatially coherent X-rays as well as the simulation and modelling of experiments using appropriately detailed physical models.


More information online: ilmt.co/PL/Z2wm 59136pr@reply-direct.com


Landmark Study Reveals How TRiC Nano Chambers Direct Protein Folding Judith Frydman, one of the study’s lead authors.


A lot of anti-cancer drugs, she added are designed to disrupt tubulin and the microtubules it forms, which are really important for cell division. So targeting the TRiC-assisted tubulin folding process could provide an attractive anti-cancer strategy.


The illustration depicts a study by SLAC and Stanford, including cryo- EM imaging (left), that discovered how a cellular machine called TRiC (right) directs the folding of tubulin (yellow tangle at the center of TRiC). Tubulin is the protein building block of microtubules that serve as the scaffolding and transport system in human cells. The results challenge a 70-year-old theory of how proteins fold in our cells and have profound implications for treating diseases linked to protein misfolding. (Credit: Greg Stewart/SLAC National Accelerator Laboratory)


Scientists have challenged a 70-year-old theory of how proteins fold in our cells, having discovered how a tiny cellular machine called TRiC directs the folding of tubulin, a protein that is the building block of microtubules, which serve as the cell’s scaffolding and transport system in humans. The results of the study could have profound implications for treating diseases linked to protein misfolding, it was suggested.


Scientists have previously thought that while TRiC and similar machines known as chaperonins provide a passive environment conducive to folding, they were not directly involved in the process.


It has been estimated that up to 10% of the proteins in human, animal and plant cells are assisted with folding within nano-chambers into their fi nal, active shapes. Many of the proteins that fold with the aid of TRiC are also intimately linked to human diseases, including certain cancers and neurodegenerative disorders like Parkinson’s, Huntington’s and Alzheimer’s diseases, said Stanford Professor


“This is the most exciting protein structure I have worked on in my 40-year career,” said SLAC/Stanford Professor Wah Chiu, a pioneer in developing and using cryogenic electron microscopy (cryo-EM) and director of SLAC’s cryo-EM and bioimaging division. “When I met Judith 20 years ago, we talked about whether we could see proteins folding. That’s something people have been trying to do for years and now we have done it.”


During the decade long study the researchers captured four distinct steps in the TRiC-directed folding process at near-atomic resolution with cryo-EM and confi rmed what they saw with biochemical and biophysical analyses.


At the most basic level, Frydman said, this study solves the longstanding enigma of why tubulin can’t fold without TRiC’s assistance: “It really is a game changer in fi nally bringing a new way to understand how proteins fold in the human cell.


“Compared to the simpler folding chambers of chaperonins in


bacteria, the TRiC in human cells is a very interesting and complicated machine,” Frydman said. “Each of its eight subunits has different properties and presents a distinct surface inside the chamber and this turns out to be really important.”


“These structural snapshots of intermediate stages in the folding sequence have never been seen before by cryo-electron microscopy,” Frydman said.


Due to the complexity of the analyses and the pandemic interlude, the study went on for so long that many of the people who worked on it have moved on to other jobs. They include postdoctoral researchers Daniel Gestaut and Miranda Collier from Frydman’s group, who carried out the biochemical part of the project and pushed it forward, and Yanyan Zhao, Soung-Hun Roh, Boxue Ma, and Greg Pintilie from Chiu’s


A SLAC-Stanford study revealed four intermediate steps in folding a human protein called tubulin, all directed by the inner walls of a cellular machine called TRiC (yellow). The process starts when a strand of tubulin enters the TRiC chamber. One end (green) hooks into the inner chamber wall; then the other end (light blue) attaches in another spot and folds, followed by the green end and two more folds of the middle sections (dark blue and red). The folding is directed by areas of electrostatic charge on the inner wall and by “tails” of protein dangling from the inner wall, which hold and stabilize the protein in the right confi guration for the next step in folding. The protein core (dark blue) contains pockets (orange) where GTP, a molecule that stores and releases energy to power the cell’s work, plugs in. (Credit: Yanyan Zhao/Stanford University)


group, who performed the cryo-EM analyses. Additional contributors included Junsun Park, a student in Roh’s group, and Alexander Leitner from ETH in Zurich, Switzerland.


The work was supported by grants to Wah Chiu and Judith Frydman from the NIH and grants to Soung-Hun Roh, who is now an assistant professor at Seoul National University, from the Korean National Research Foundation and Suh Kyungbae Foundation (SUHF).


More information online: ilmt.co/PL/JkJg and:ilmt.co/PL/d1DB 59619pr@reply-direct.com


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