Babraham Institute director Professor Michael Wakelam dies after suspected coronavirus infection
Professor Michael Wakelam, the director of the Babraham Institute, has died following a suspected coronavirus infection.
The eminent scientist and married father of two suffered respiratory complications arising from the infection, the institute said. He was in his mid-60s.
The institute, a world-leading centre of biological research, said it was “devastated”.
“Professor Wakelam’s warm personality and care for others were reflected in his leadership of the institute. His loss will be felt widely across the scientific community and by all those who knew him,” the institute said in a statement following his death on March 31.
Born in 1955, he completed a BSc in medical biochemistry in 1977 at Birmingham University, where he also completed his PhD in biochemistry in 1980.
He was a post-doc at the University of Konstanz in Germany and, as a Beit Memorial Fellow, at Imperial College London, before being appointed to a lectureship in biochemistry at Glasgow University in 1985.
He returned to Birmingham in 1993 as professor of molecular pharmacology in the Institute for Cancer Studies, before joining the Babraham Institute as director in 2007.
“Professor Wakelam brought a dedication to scientific expertise, both in creating and protecting the environment required for excellent science to happen, and in creating an environment that developed expertise and capabilities in each individual to allow them to achieve their best,” said the institute.
“He was passionately committed to providing an excellent training experience for the institute’s PhD students. Michael was an active voice on the value of fundamental research and international science. His research passion was lipids (cellular fats) and the techniques used to study them, and he maintained a research lab and lipidomics facility at the Institute during his time as director.”
It added: “Professor Wakelam was a strong advocate of the power of uniting academic and commercial research, as exemplified by the fruitful partnerships that exist today between the institute’s academic research and the commercial research community of the Babraham Research Campus.
“He enjoyed the opportunities his work brought in meeting and connecting with others, including representing the Institute as part of the EU-LIFE alliance of research institutes.”
Professor Wakelam is survived by his wife Jane and their two sons Alex and Patrick.
He was the honorary professor of lipid signalling in the Cambridge University Clinical School, an honorary professor at the University of Birmingham and a visiting professor at King’s College London. He was a fellow of the Royal Society of Biology and a member of the Academia Europaea, which acts as co-ordinator of European interests in national research agencies.
In 2018, he received the Morton Lectureship from the Biochemical Society.
Professor Wakelam spent more than 20 years researching cell signalling and communication.
A particular focus was the use and development of advanced lipidomics methodologies to determine the functions of individual lipid molecular species in the regulation of signalling pathways in normal and cancer cells and in inflammatory responses.
The institute has opened a book of remembrance for anyone who would like to share their memories of Prof Wakelam and tributes to him.
These can be emailed to comms@babraham.ac.uk and they will be collected together and shared with his family.
Brilliant and affable
I had the privilege and pleasure of interviewing Prof Wakelam about his work in 2018, writes Paul Brackley.
I spoke to him about research into the common cold - part of pioneering lipidomics work designed to help us better understand, and ultimately, combat this nuisance.
And when I interviewed him, he had a streaming cold of his own.
“I thought you’d appreciate that irony,” he laughed.
He was generous with his time, affable, clearly a brilliant scientist and thoroughly entertaining.
His loss will be felt very keenly by all those who knew him.
Below, we reproduce that article in full.
Bless you... a step towards a cure for the common cold
November 2018
Professor Michael Wakelam, director of the Babraham Institute, has been leading efforts to understand how to stop the rhinovirus in its tracks, as he explained to editor Paul Brackley
Got the sniffles?
You’re in good company. Professor Michael Wakelam, director of the Babraham Institute, is battling a streaming cold when we discuss his latest research… into colds.
“I thought you’d appreciate that irony,” he laughs.
In time, the pioneering work he has been leading at Babraham may help put an end to the sheer nuisance of the ubiquitous common cold.
Adults can expect, on average, two to four of them a year, while children typically succumb six to eight times annually.
By the age of 75, it’s likely you’ll have experienced about 200 colds – spending two and a half years of your life dealing with a runny nose, sore throat, coughs and sneezes. That’s a lot of tissues.
There is, of course, no cure. Although colds are big business – estimates suggest there are a billion of them in the US each year, and 22 million school days are lost annually as a result of them – no pharmaceutical company has been able to develop a curative therapy.
Instead, the myriad of cold ‘remedies’ available deal with the symptoms, not the cause, or rather causes, as there are a couple of hundred viruses out there that lead to a cold.
The most common of these are rhinoviruses, of which there are about 160 types.
Prof Wakelam, working with scientists at the National Heart and Lung Institute at Imperial College London, has been tackling one, and not just with Lemsip.
Using an approach called lipidomics, the researchers have been examining the array of lipids, or fat molecules, found in all cells to examine the changes caused in them by the rhinovirus. Selecting inhibitors that can prevent these changes, they have been able to stop the virus replication in its tracks, limiting further infection.
“A virus gets into a cell either through a receptor, or other internalisation mechanism,” he explains. “It gets across the cell membrane. When it’s in the cell, it replicates.
“There are various mechanisms by which viruses do that but fundamentally it hijacks our cells’ normal machinery. It interacts with membranes inside the cell and is then released, going through the plasma membrane to get out and infect other cells.”
Membranes are made up a range of lipid – or fat – molecules.
“There’s a series of classes of lipids which have a chemical similarity but which are also distinguished by different chemistry within them.
“We came up with the view that if viruses are getting into cells and affecting membranes, they must be doing that for a very specific reason. So let’s determine what happens to the lipids within the cellular membranes when infected with the virus.”
Using bioinformatics techniques, the team then aimed to predict what enzymes are bringing about the changes in lipids, thereby identifying potential targets for cold-busting drugs.
“This has only become possible to do in the last few years because we and other labs internationally have developed methods that enable us to determine all of the lipids within a cell,” says Prof Wakelam.
“The astonishing fact is that there are potentially 20,000 different individual lipid molecules within a human cell, so the chemical variability is enormous. There are probably up to a dozen different classes but within each there are multiple chemical species which gives you a diversity that we hadn’t fully appreciated until a few years ago.”
Mass spectrometry has enabled scientists to identify each of these molecular species.
“We were able to follow, using computational biology techniques, changes in the individual molecules, rather than just the classes,” says Prof Wakelam. “This enabled us to pick up the differences induced in the cells by the infection, which allowed us to identify particular molecular targets.
“We took primary human bronchial-epithelial cells, which are normally present in your lung and grew them in tissue culture. We infected the cells with the virus and determined the changes in the lipids each hour for a seven hour period, thus this was a very acute effect.”
When a cold virus invades our cells, it leads to a chemical change in the lipids, most of which have acyl chains or ‘fatty acids’. The virus can induce modifications in lipids including changing the length of these fatty acid chains and the number of double bonds. It is these double bonds between carbon atoms that make fat ‘unsaturated’. Fats where each carbon is bonded to two hydrogens are said to be saturated.
And just as butter is different to margarine because of its saturated fat content, so the membranes made from our cellular lipids have different physical properties when they are altered by the virus.
“The viruses appear to be inducing changes in the activity of some of the enzymes we call elongases or desaturases, which affect the chemical structure of the fatty acid,” explains Prof Wakelam.
“The consequence is that it changes the membrane, making it more fluid so proteins can move through the membrane more easily, or makes it more rigid, or more curved, and therefore it changes its properties. This allows viruses to get in and out or proteins to move around the membrane which are interacting with the virus.”
By targeting enzymes – protein molecules in our bodies that act like catalysts and bring about these changes – the researchers believe it could be possible to stop the virus in its tracks.
“We took some molecules that were commercially available, added them to cells in culture and looked at whether they blocked viral replication, and a number of them indeed did, so we managed to prove the principle,” says Prof Wakelam. “We wondered whether it would block the entry of the virus into the cells. With the rhinovirus, the molecules we tested didn’t block entry, but it blocked the ability of the virus either to replicate or to be released from the infected cell and infect an adjacent cell.”
But Prof Wakelam warned that we are some way off identifying an appropriate medicine.
“The molecules are not ones you would want to give to a human at the moment because they are developed for laboratory use but what they did is prove that particular enzymes are potential targets in this case.
“These targets need to be worked up and molecules identified. We need to identify a pharmaceutical partner who wants to investigate this from a drug development standpoint or biotech partner interested in looking at these type of enzymes.”
Stopping the infection would allow the immune system to wind down its response. The symptoms we experience when we get a cold are the body’s own attempt to rid us of the virus.
A runny nose, for example, is cause by the mucus membranes in our nose producing excess mucus to stop the infection spreading further into the lungs and respiratory tract.
The research was conducted with a rhinovirus called RV-A1b, but there are indications that the approach will work more widely.
“We think the same mechanisms will apply with other viruses. Using this paradigm we should be able to predict enzymes that are novel therapeutic targets,” says Prof Wakelam.
Targeting the enzymes, rather than the virus itself, also solves another potential problem – evolution.
Each year a new vaccine has to be developed to tackle the latest strain of the influenza virus as it evolves. The vaccine provokes the body into producing antibodies that lock on to the virus. Rhinoviruses also evolve, albeit not as fast or as extensively.
“With influenza what’s evolving is small changes in the surface molecules of the virus so you have to change the vaccine each year,” says Prof Wakelam.
“The influenza virus, irrespective of that mutation, still enters the target cell in the same way.
“So with this type of approach, we have a means of treating the virus that is not dependent on an antibody response and therefore is not necessarily affected by the chemical modification of the virus.”
Indeed, the development of more sophisticated lipidomics techniques opens the door to a new area of research.
While proteins, which act as our cell machinery, and our genes have been well studied, lipids have been thought of as having a largely structural role. Now, there is the opportunity to explore their role in viral infection.
“We’ve seen fantastic progress in the study of genes and proteins over recent decades and this has had some major impacts on our understanding of human biology, health and ageing. “Yet, lipids represent a phenomenally complex and important component of cells that we are still only beginning to understand,” says Prof Wakelam.
“There are many more discoveries to be made with the help of lipidomics and it has great potential to change what we know about our own cells.”
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