As previously notified, John Trinick, Professor of Animal Cell Biology, died on 15 January 2019. The following tribute has been contributed by his family, friends and former colleagues.
Professor John Trinick was born in 1945, and by the age of 16 he had been to nine different schools across Yorkshire and the South East of England. He didn’t find school easy, and he failed his 11+ exam, which had a lasting impact on him.
Where many young people in the same position then found it hard to get into academia, John was lucky to have a truly inspirational teacher, Peter Walker at Scarborough Technical College, who imbued him with a lifelong passion for science and a belief that anything is possible with enough hard work.
After completing his A levels in 1966, John got a place at the University of Leicester to study for a B.Sc. in Physics, and then for a PhD in Biochemistry with Dr Arthur Rowe that started his career in muscle research, developing methods to purify thick filaments from rabbit muscle. He then worked on thick filament proteins as a postdoctoral fellow from 1973 in the laboratory of Professor Susan Lowey at Brandeis University in Massachusetts, where he also first met his best friend, Dr John Holt.
John returned to the UK in 1976, where he worked on thick filaments, myosin and actin-myosin interactions with Gerald Offer and Arthur Elliott at King’s College London in the Biophysics Department and MRC Biophysics Unit on Drury Lane.
Leaving London, John moved to Langford in the West Country where he set up an independent laboratory in the then Agricultural Research Council Meat Research Institute in the bucolic grounds of Bristol University’s veterinary school. Here, despite the applied research direction of the Institute, he continued fundamental research, in part funded by grants from the American Muscular Dystrophy Association. This led to a series of papers on the structure and behaviour of myosin revealed by negative staining electron microscopy, working with Matt Walker. He also performed pioneering work on cryo-electron microscopy, obtaining the first images of actin filaments in the hydrated state, working with Matt Walker and Howard White. However, he also published an applied paper with Gerald Offer on the basis of the water-holding properties of meat that has, to date, received 588 citations.
In 1990 the Institute closed, and while short term funding allowed John to remain at Langford, the future became uncertain and John began to look for other jobs. After coming close to relocating to Houston and Edmonton, in 1997 he received a well-deserved appointment to a Chair at Leeds University, a position he held until his death.
John was an author of over 100 research papers, many in high impact journals. He was keen to work on only the most important topics. As a biochemist, much of his research was on protein structure and, as a physicist, he increasingly took advantage of the remarkable advances in electron microscopy that allowed the near-atomic structure of a protein to be found without having to crystallise it.
John's studies focused mainly on the muscle proteins titin and myosin. Titin is by far the largest known protein. Strands of titin consisting of multiple motifs of 100 amino acid residues run along the surface of the thick filaments of muscle and continue on to link these filaments to the Z-disc. They thereby contribute to the stiffness of muscle even at rest. John was among the first to devise methods to purify native titin, characterize its structure, and show its arrangement within muscle.
John was the first to propose that titin acts as a ruler – ensuring that the myosin filaments are precisely constant in length. Working on sabbatical at EMBL in Heidelberg, he and his collaborators analyzed the sequence of titin and showed that the pattern repeated every 11 motifs, which is the same distance along titin as that of the underlying myosin repeat, strongly supporting John's hypothesis that titin was a molecular ruler. John and his long-standing friend and colleague Larissa Tskhovrebova were able to image individual titin molecules when they were stretched on drying, and they observed that one region with a special sequence was particularly elastic. This region varies greatly in length in different muscles, accounting for their different mechanical properties. John also initiated, and successfully accomplished, studies of titin elastic properties at a single molecule level. This work was achieved in Leeds with Larissa Tskhovrebova, and their colleagues back at King’s College London, Bob Simmons and John Sleep. It broke new ground for mechanical studies of protein elasticity, with the resulting publication attracting attention of the scientific community far beyond muscle, and forming a basis for a new era in protein research.
All but one of the intermediates in the ATP-fuelled crossbridge cycle of muscle that generates force are relatively well defined. However, there is an important gap in our knowledge. The structure of the complex of myosin with actin that is formed just prior to the step that produces force has yet to be determined. In the 1980’s, John and Howard White started a long-term project to determine this structure. Using some of the prototype cryo-EM equipment, they evolved the technique of rapidly mixing myosin during ATP hydrolysis with actin, and stopping the reaction at chosen times of the order of milliseconds by spraying the mix onto EM grids, rapidly plunging them into liquid ethane at about -180 °C, and examining the still-frozen grids in the EM. They overcame many technical obstacles to observe the initial complexes formed. Their observations were made at a relatively low resolution that did not reveal the details of the structural changes at the molecular level, but advances in cryo-electron microscopy make it likely that this work will lead to high resolution structures of these intermediates.
John's publications reflect the worldwide collaborations he made, including those with Gerald Offer, Peter Knight, Matt Walker, Larissa Tskhovrebova, Jim Sellers and Howard White, that spanned several decades. As a physicist, he found new physical techniques appealing, and with his collaborators he studied many aspects relating to the question of how cells other than muscle were able to be motile. He studied variants of myosin other than the archetypal myosin in muscle, as well as rotary motors.
John’s papers and seminars were models of clarity, presenting concise and compelling arguments. His skills as a scientist were in identifying critically important problems and, if no methods were available to solve them, he would develop them himself. He always advocated for accuracy and brevity with his colleagues, friends, and family alike.
John had a wide range of scientific interests and would frequently send his colleagues emails with a subject line “thought that this might interest you” which contained recent publications in muscle research or, equally likely, physics, or astronomy.
John met his wife, Jennifer, in Leicester and they have three children, Leo, Ros and Fay. The family fell in love with the Outer Hebrides 30 years ago, and have spent many happy holidays walking on the beaches and sailing around the islands. John loved the outdoors. He and Jennifer would often walk in the hills above Ilkley and cycle around the Dales on their tandem. He also had an astonishing knowledge of, and interest in, English literature – taking great pleasure in poetry ranging from Larkin and Keats to the First World War Poets, and in the works of Joseph Conrad.
John will be hugely missed by family, friends, and colleagues.