2025 Research Retreat

The whole McDonnell Group was at the Research Retreat in Canary Wharf this year! A strong showing with both Keira and Imogen presenting posters. We even had time to take the first official lab picture! It was a fantastic day, with lots of great science and congrats to all the speakers, special shout out to our fellow ARR ECRs Dr George Robinson, Dr Lizzy Rosser and Dr Claire Beesley.

L to R: Dr Thomas McDonnell, Ms Keira Louden, Ms Imogen Buckle, Ms Lucia Martin and Dr Christophe Lalaurie.

New Paper Published Sheds Light on The Structure of B2GPI

We are happy to share this new paper from the McDonnell Lab!

This paper was a real collaborative effort from all involved including Prof. Thalassinos, Prof Dalby and Prof. Delcea who really helped throughout. Also very pleased to see Dr Bradford and Dr Lalaurie's work come to fruition in this paper:

https://www.jthjournal.org/article/S1538-7836(25)00111-4/fulltext

Figure 3: Ion mobility mass spectrometry and FACs analysis. (A) The spectra of both the nonclipped β2-glycoprotein I (β2GPI; top) and the plasmin-clipped β2GPI (bottom), as can be seen, both retain a number of glycoisoforms; however, the Gaussian distribution of peaks is significantly different in the plasmin-clipped β2GPI, suggesting a significant change. A significant shift in charge in the peaks is also seen, likely due to the removal of the terminal 8 amino acids containing significantly charged species (1 lysine and 2 aspartic acid residues). A zoom-in demonstrates the shift in species, again confirming that a modification has taken place. (B) Further to this, ion mobility data show that in nonclipped β2GPI, there are 2 populations of structures, with the dominant structure being the earlier peak. In contrast, plasmin-clipped β2GPI shows a single dominant structure, with the peak moving fractionally to the right, suggesting that cleavage not only removes 1 structure but may alter the remaining form. The top figure demonstrates commercial (Com) β2GPI, healthy (HC) β2GPI, and clipped β2GPI, while the bottom selects just the HC and Cl β2GPI. The clipped β2GPI is generated from this HC pool; as such, this comparison emphasizes the structural shift under cleavage conditions. Direct comparison of commercial and purified B2GPI can be seen in Supplementary Figure S3. (C) Plasmin-clipped β2GPI is known to lose its ability to bind to cell surfaces; as such, we conducted FACS with fluorescently labeled β2GPI (Cl and nonclipped) on human umbilical vein endothelial cells. As can be seen, nonclipped β2GPI (Cy5 labeled) bound to approximately 3% to 35% of cells (2 μg β2GPI, 500 000 cells) while plasmin-clipped β2GPI bound between 0% and 4.5% of cells, which was significantly less. ATD, arrival time distribution; FACS, flow cytometry.

The paper investigates how plasmin, a key enzyme in the fibrinolytic system, interacts with β2-glycoprotein I (β2GPI), a protein implicated in antiphospholipid syndrome (APS). The study demonstrates that plasmin cleaves β2GPI, leading to structural modifications that affect its binding affinity to pathogenic antibodies associated with APS. These findings provide insights into the molecular mechanisms underlying APS and suggest potential therapeutic targets for managing this autoimmune disorder.

We would like to thank the Medical Research Foundation, and Versus Arthritis for their funding through the McDonnell Lab for this project.

The Versus Arthritis Fellows Day

The McDonnell group attended the Versus Arthritis Fellows meeting with members of the ARR department at UCL, had a great time with really interesting talks and so exciting to see the next generation of talented rheumatologists and scientists coming through focussing on MSK disease. You definately leave these events with more ideas of how to leverage cutting edge approaches to help patient outcomes.

ARR Department at the VA Fellows Day 2025, L to R: Dr Junjie Peng, Dr George Robinson, Dr Beth Goulden, Prof. David Isenberg, Dr Venkat Reddy and Dr Thomas McDonnell.

It was especially inspiring to hear the patient talk (a highlight every year) highlighting the difficult diagnostic and therapeutic journey of patients with MSK diseases and again emphasising the need for new diagnostic tools and therapeutic stratification. Also a great session on patient engagement and how important it is not just to engage patients but really involve them in your research.

It was great to see some old friends from other institutes (ICH, QMUL) and make some new ones over dinner! An inspiring two days in Loughborough and already looking to the next!