The latest Business updates from the science industry


by Heather Hobbs Elusive Missing Step in Photosynthesis Cycle Captured


what happens in the fi nal moments leading up to the release of breathable oxygen. The results are helping scientists develop artifi cial photosynthetic systems that mimic photosynthesis to harvest natural sunlight to convert carbon dioxide into hydrogen and carbon-based fuels.


“The more we learn about how nature does it, the closer we get to using those same principles in human-made processes, including ideas for artifi cial photosynthesis as a clean and sustainable energy source,” said co-author Jan Kern, a scientist at Berkeley Lab.


Co-author Junko Yano, also at Berkeley Lab, said, “Photosystem II is giving us the blueprint for how to optimise our clean energy sources and avoid dead ends and dangerous side products that damage the system. What we once thought was just fundamental science could become a promising avenue to improving our energy technologies.”


Using SLAC’s X-ray laser, researchers have fi nally seen the process by which nature creates the oxygen we breathe (Credit: Greg Stewart SLAC National Accelerator)


Crucial in shaping and sustaining life on Earth some aspects of how photosynthesis works are still unclear. One of these mysteries includes how Photosystem II, a protein complex in plants, algae and cyanobacteria, harvests energy from sunlight and uses it to split water, to produce the oxygen we breathe.


Now researchers from the Department of Energy’s SLAC National Accelerator Laboratory and Lawrence Berkeley National Laboratory, together with collaborators from Uppsala University, Humboldt University and other institutions have succeeded in cracking a key secret of Photosystem II.


Using SLAC’s Linac Coherent Light Source (LCLS) and the SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan, the researchers were able to see for the fi rst time in atomic detail


During photosynthesis, Photosystem II’s oxygen-evolving centre – a cluster of four manganese atoms and one calcium atom connected by oxygen atoms – facilitates a series of challenging chemical reactions that act to split apart a water molecule to release molecular oxygen.


The centre cycles through four stable oxidation states, known as S0 through S3, when exposed to sunlight. Likening this to a baseball fi eld scenario S0 would be the start of the game when a player on home base is ready to go to bat. S1-S3 would be players on fi rst, second and third. Every time a batter connects with a ball, or the complex absorbs a photon of sunlight, the player on the fi eld advances one base. When the fourth ball is hit, the player slides into home, scoring a run or, in the case of Photosystem II, releasing one molecule of breathable oxygen.


In their experiments, the researchers probed this centre by exciting samples from cyanobacteria with optical light and then probing them with ultrafast X-ray pulses from LCLS and SACLA. The data


revealed the atomic structure of the cluster and the chemical process around it.


Using this technique, the scientists for the fi rst time imaged the mad dash for home – the transient state, or S4, where two atoms of oxygen bond together and an oxygen molecule is released. The data showed that there are additional steps in this reaction that had never been seen before.


“Other experts argued that this is something that could never be captured,” said co-author Uwe Bergmann, a scientist and professor at the University of Wisconsin-Madison. “It’s really going to change the way we think about Photosystem II. Although we can’t say we have a unique mechanism based on the data yet, we can exclude some models and ideas people have proposed over the last few decades. It’s the closest anyone has ever come to capturing this fi nal step and showing how this process works with actual structural data.”


The new study is the latest in a series undertaken by the team over the past decade.


“Most of the process that produces breathable oxygen happens in this last step,” said co-author Vittal Yachandra, a scientist at Berkeley Lab. “But there are several things happening at different parts of Photosystem II and they all have to come together in the end for the reaction to succeed. Just like how in baseball, factors like the location of the ball and the position of the basemen and fi elders affect the moves a player takes to get to home base, the protein environment around the catalytic centre infl uences how this reaction plays out.”


Based on these results, the researchers plan to conduct experiments designed to capture many more snapshots of the process.


More information online: ilmt.co/PL/x4q1 60635pr@reply-direct.com


Cellular Controllers Captured in Action


A team of international researchers led by Professor Davide Calebiro from the University of Birmingham, have used advanced microscopy to understand the role of beta-arrestin molecules in controlling activity of G protein-coupled receptors (GPCRs) the largest group of receptors in the human body.


GPCR’s mediate the effects of many hormones and neurotransmitters and as a result, are major targets for drug development; between 30- 40% of all current therapeutics are against these receptors. Once the receptors are activated, beta-arrestins dampen the signal in a process called desensitisation but can also mediate signals of their own.


The new study has unexpectedly revealed that beta-arrestins attach themselves to the outer cell membrane waiting for hormones or neurotransmitters to land on receptors. Surprisingly, the interactions between beta-arrestins and active receptors are much more dynamic than previously thought, allowing for a far better control of receptor-mediated signals.


Davide Calebiro, Professor of Molecular Endocrinology in the Institute of Metabolism and Systems Research at the University of Birmingham and Co-Director of the Centre of Membrane Proteins and Receptors (COMPARE) of the Universities of Birmingham and Nottingham said: “In our study, we used innovative single-molecule microscopy and computational methods developed in our lab to observe for the fi rst time how individual beta-arrestin molecules work in our cells with unprecedented detail.


“We have revealed a new mechanism that explains how beta-arrestins can effi ciently interact with receptors on the plasma membrane of a cell. Acting like air traffi c controllers, these proteins sense


when receptors are activated by a hormone or a neurotransmitter to modulate the fl ow of signals within our cells. By doing so, they play a key role in signal desensitisation, a fundamental biological process that allows our organism to adapt to prolonged stimulation.


“These results are highly unexpected and could pave the way to novel therapeutic approaches for diseases such as heart failure and diabetes or the development of more effective and better tolerated analgesics.”


This success is attributed to the COMPARE environment, a world- leading research centre for the study of membrane proteins and receptors that brings together 36 research groups with complementary expertise in cell biology, receptor pharmacology, biophysics, advanced microscopy and computer science.


The novel single-molecule microscopy and computational approaches developed in this study could provide a signifi cant new tool for future drug development, allowing researchers to directly observe how therapeutic agents modulate receptor activity in living cells with unprecedented detail. In the future, COMPARE researchers led by Professor Calebiro plan to further automate the current pipeline so that it can be used to screen for novel drugs such as biased opioids currently in development for the treatment of pain.


Dr Zsombor Koszegi, who shares fi rst co-authorship of the study with Dr Jak Grimes and Dr Yann Lanoiselée, said: “Being able to see for the fi rst time how individual receptors and beta-arrestins work in our cells was incredibly exciting. Our fi ndings are highly unexpected and bring our understanding of the way beta-arrestin coordinates receptor signalling to a whole new level, with major implications for cell biology and drug discovery.”


The research was funded by the Wellcome Trust, Medical Research Council and the DBT/Wellcome Trust India Alliance.


The study was published in Cell More information online: ilmt.co/PL/QeNK


60638pr@reply-direct.com


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56