I defended my PhD 10 years ago today. That was the least remarkable thing that happened that day. Sharing something I wrote about it last year. Since then "the horrors persist but so do we." And with dignity.
Mackenzie, @waldronlab.bsky.social et al. argue that differing superoxide dismutase metal preferences observed across the tree of life evolved through tuning of their redox properties by the secondary coordination sphere.
🔗 doi.org/10.1093/molbev/msag040
#evobio #molbio
And appreciation also to the funders of this work: BBSRC (UK), NIH (US) and @ncn.gov.pl (Poland). An international and multidisciplinary effort.
Huge thanks to the team members on the study: Kacper and Eilidh, during my time in Newcastle, and Rafał from the Warsaw team. Also, to collaborators Arnaud, who helped with the crystallography, and long-time US collaborator Thomas Kehl-Fie.
The latest publication from the lab is now available to read online at Molecular Biology and Evolution here: academic.oup.com/mbe/advance-...
Nonetheless, our evolutionary analysis shows that the S. aureus cambialistic SodFM (confusingly named SodM) is under purifying selection, including the residues that control metal-preference. So its cofactor flexibility has actually been selected, presumably during the emergence of pathogenicity.
This shows that the two preferences are intrinsically linked. To increase the Mn activity, you necessarily reduce the Fe activity, and vice versa, as one would expect in the redox tuning model. Cambialism represent a compromise – flexibility but lower activity.
When we combined the data from our analysis of a whole load of SodFM variants, we observed this remarkable correlation between metal preference (cambialism ratio; Fe-activity / Mn activity) and redox properties.
These data showed that the redox properties of SodFMs really do change, when a SodFM changes its metal-preference. Either through evolutionary shifts, or when we create synthetic mutated variants with altered metal-preference.
So instead, we used simple redox spectra as a proxy. We used spectra to measure the extent to which the metal is oxidised vs reduced, when at equilibrium in an aerobic solution (termed nOS), compared to the fully oxidised/reduced spectra.
Testing the redox tuning model in SodFMs is hard. The ion is buried in the structure, so it’s not possible to measure the reduction potential in vitro, which requires interaction between the redox centre and an electrode.
A model for how such changes in catalytic metal-preference can occur, in an enzyme that needs a redox-active metal cofactor, is through ‘redox tuning’. Here, the second sphere modulates the reduction potential of the ion through outer sphere interactions.
More recently still, we studied the evolution of the whole SodFM family, and found that such changes in catalytic metal-preference were frequent, with examples found all over the SodFM tree: doi.org/10.1038/s415...
Structure of the active site of the S. aureus SodFMs, illustrating three residues in the secondary coordination sphere that control metal-preference.
Then we studied that pair in biochemical detail to identify residues in the metal’s secondary coordination sphere that had changed during neofunctionalisation to change its metal-preference: doi.org/10.1038/s414...
We previously showed that one of a pair of SodFMs in S. aureus has undergone recent evolution to switch from Mn-preferring to cambialistic, helping this pathogen to overcome Mn starvation during infection of the host: doi.org/10.1371/jour...
Structure of a pair of SodFM isozymes from S. aureus, which display different catalytic metal-preferences.
SodFMs come in three ‘flavours’ based on the metal specificity of their catalysis: they can be highly Mn-preferring (inactive with Fe), highly Fe-preferring (inactive with Mn), or ‘cambialistic’ (active with either metal). Yet they all have the same structure.
New paper alert! Just out, the latest in our study of the evolution of a fascinating family of metalloenzymes, the iron- or manganese-dependent superoxide dismutases (SodFMs). Here, we’ve probed the evolutionary mechanism.
Grant rejected 27/11/2025
Grant successful 28/11/2025
The ups and downs of academic life: a story told in two Acts (from two consecutive days)
A cracking weekend in Annecy with a whole load of old friends and their families. Good times.
Even a >3 h delay to my flight back from Geneva can’t dampen my spirits.
The survivors
The team's medals
Waiting their turn
Warming up together
On Saturday, we gathered two teams from IBB-PAS to run the Relay Marathon #Ekiden in Warsaw. It was a good day for running, but it made for a sore Sunday (for me, at least). Thanks to all of our runners for a great team effort!
Finally, we're recruiting!
If you'd like to do a PhD using NMR structures to study the dynamics of a metalloenzyme, then you're in luck! Come to Warsaw for this project, in collaboration with Simone Ciofi-Baffoni's group at CERM, Florence: ibb.edu.pl/app/uploads/...
Another manuscript, with Paola Massari's group at Tufts, is now on BioRXiv. We characterised the copper storage protein from Neisseria gonorrhoeae, which is important in its periplasmic copper homeostasis but is also a potential vaccine candidate: doi.org/10.1101/2025...
Last week we had a manuscript accepted, a collaboration paper with Xingxiang Chen's group in Nanjing. We studied the mechanism by which the fungal toxin fumonisin B1 (FB1) damages vascular epithelia cells. You can read the open access article here: doi.org/10.1016/j.cb...
Lots of new stuff to share today...
This photograph captures Sir David Attenborough seated outdoors on the rugged terrain of Skomer Island. Behind him, the ocean and coastal cliffs form a scenic backdrop under a clear sky. Sir David, dressed in a khaki jacket and light trousers, looks towards the camera with a gentle expression, exuding a sense of warmth, calm, and wisdom. Around him, puffins can be seen flying and perched on the rocky ground, illuminated in rays of golden sunlight as the sun sets behind the cliffs.
Happy 99th birthday to the man who gave voice to the wild. 🎉
Sir David Attenborough, thank you for a lifetime dedicated to the natural world, and for sharing its story with wisdom, wonder, and grace.
You've inspired generations to fall in love with nature.
Original 1925 jacket cover of The Great Gatsby The Great Gatsby Here is a novel, glamorous, ironical, compassionate a marvellous fusion into unity of the curious incongruities of the life of the period which reveals a hero like no other one who could live at no other time and in no other place. But he will live as a character, we surmise, as long as the memory of any reader lasts. "There was something gorgeous about him, some heightened sensitivity to the promises of life. .. It was an extraordinary gift for hope, a romantic readiness such as I have never found in any other person and which it is not likely I shall ever find again?" It is the story of this Jay Gatsby who came so mysteriously to West Egg, of his sumptuous er-tertainments, and of his love for Daisy Buchanan a story that ranges from pure lyrical beauty to sheer brutal realism, and is infused with a sense of the strangeness of human circumstance in a heedless universe. It is a magical, living book, blended of irony, romance, and mysticism. CHARLES SCRIBNER'S SONS The GREAT GATSBY FITZGERALD
They were careless people, Tom and Daisy- they smashed up things and creatures and then retreated back into their money or their vast carelessness or whatever it was that kept them together, and let other people clean up the mess they had made.
-FS Fitzgerald, The Great Gatsby, published 4/10/1925.
Prediction:
Today (4/9/25) registered the greatest ill gotten gains from insider trading in history.
Yes, that's the job of a PI, I suppose.
I can't complain too much as I managed to avoid writing one for the last couple of years (bliss!), so it's about time I got back to the task.
Grant number 2 submitted for this calendar year.
Two down, two more to go.
But for now, on to the manuscripts that have been backing up for the last couple of months.
Florence never fails to take your breath away