IMS Highlighted Publications

Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells

Cao H, Neerincx A, de Bono B, Lakner U, Huntington C, Elvin J, Gudgin E, Pridans C, Vickers M, Huntly B, Trowsdale J, Barrow A:  British Journal of Haematology 2021; 193: 946-950

Summary

Cancer treatment has made great strides in recent decades, especially in recruiting the immune system to the fight.   A major success has been the so-called “check-point inhibitors”, which unblock immune checkpoints that cancers manipulate in order to dampen down immune reactions they might provoke.  Siglec-15 is a newly discovered immune checkpoint found to be expressed almost exclusively on the surface of solid tumour cells.  Its discovery parallels the key immune check point PD-L1 and has recently received much attention.  Siglec-15 antibody therapy is now proceeding into clinical trials. Our work uncovers another aspect of this molecule in cancer therapy.  We found that in one type of leukaemia that affects the elderly, acute myeloid leukaemia (AML), Siglec-15 is highly expressed compared to healthy cells.  Furthermore, the Siglec-15 on these AML cells can help to rapidly engulf antibodies against Siglec-15.  These two key properties of Siglec-15 make it possible that anti-Siglec-15 might be used as a “magic bullet” to treat AML cells by introducing toxins into the diseased cell. The “magic bullet” and the “check-point inhibitor” approaches showcase two exciting arms of Siglec-15 therapies in the fight against both solid tumours as well cancers of the blood.    

Our Postdoc first name paper this month is Dr Virtu Solano Collado

Recognition of streptococcal promoters by the pneumococcal SigA protein.

Solano-Collado V, Ruiz-Cruz S, Lorenzo-Díaz F, Pluta R, Espinosa M, Bravo, A., In: Frontiers in Molecular Biosciences 2021; 8: 14: 666504.

Summary

Bacteria in their natural habitats are often exposed to rapid environmental changes and they need to modulate gene expression to adapt to these changes. This is achieved with the help of a protein complex (six different proteins) known as the RNA polymerase. One of these proteins is called the sigma factor and it responsible for directing the complex to the promoter regions of the genes that need to be transcribed depending on the bacterial needs. In the case of the Gram-positive pathogenic bacterium Streptococcus pneumoniae, most promoters are recognized by SigA, a poorly studied sigma factor.  In this work, we wanted to get insight into the role of this protein. . Using this purified protein, we were able to reconstitute a fully active RNA polymerase (RNAP-SigA) capable of recognizing specific promoters, not only from the pneumococcal chromosome but also from a plasmid called pMV158 which carries antibiotic resistance genes and can replicate in different bacterial species (broad-host range). This is important as RNAP-SigA recognizes the promoters of genes that are required for the replication and the mobilization (i.e. the capacity to be transferred from bacterium to bacterium) of this plasmid. This tells us that SigA contributes to the broad-host range of this plasmid and consequently to the spread of antibiotic-resistance genes among bacteria.

Computational biomechanical modelling of the rabbit cranium during mastication

Watson, P. J., Sharp, A., Choudhary, T., Fagan, M. J., Dutel, H., Evans, S. E. & Gröning, F.:  Scientific Reports. 11, 13196.

Summary

The relationships between mechanical forces and bone structure are well known in weight-bearing bones such as the femur. In the skull, form-function relationships are less obvious, but understanding how skull bones adapt to mechanical forces is relevant for maxillofacial surgery and dentistry. To date, this research area has relied to a large degree on animal experiments, with the rabbit being one of the most common animal models. In this study, we combined in silico methods of multi-body dynamics and finite element analysis to simulate biting and chewing in the rabbit, and to predict the resulting strains in the skull bones. Our novel computational models have shed light on the mechanical adaptation of skull features and have the potential to help replacement, refinement, and reduction (3Rs) of animal experiments in this research area.

International educators’ attitudes, experiences, and recommendations after an abrupt transition to remote physiology laboratories

Julia Choate, Nancy Aguilar-Roca, Elizabeth Beckett, Sarah Etherington, Michelle French, Voula Gaganis, Charlotte Haigh, Derek Scott, Terrence Sweeney, and John Zubek in: Advances in Physiology Vol 45; 2

^{This is a collaboration between University of Aberdeen and international collaborators from UC Irvine, Scranton, Michigan, Toronto, Monash, Leeds, Flinders, Adelaide, Murdoch.}

Summary: 

The COVID-19 pandemic triggered university lockdowns, forcing physiology educators to rapidly pivot laboratories into a remote delivery format. This study documents the experiences of an international group of 10 physiology educators surrounding this transition. They wrote reflective narratives, framed by guiding questions, to answer the research question: “What were the changes to physiology laboratories in response to the COVID-19 pandemic?” These narratives probed educators’ attitudes toward virtual laboratories before, during, and after the transition to remote delivery. Thematic analysis of the reflections found that before COVID-19 only a few respondents had utilized virtual laboratories and most felt that virtual laboratories could not replace the in-person laboratory experience. In response to university lockdowns, most respondents transitioned from traditional labs to remote formats within a week or less. The most common remote delivery formats were commercially available online physiology laboratories, homemade videos, and sample experimental data. The main challenges associated with the rapid remote transition included workload and expertise constraints, disparities in online access and workspaces, issues with academic integrity, educator and student stress, changes in learning outcomes, and reduced engagement. However, the experience generated opportunities including exploration of unfamiliar technologies, new collaborations, and revisiting the physiology laboratory curriculum and structure. Most of the respondents reported planning on retaining some aspects of the remote laboratories postpandemic, particularly with a blended model of remote and on-campus laboratories. This study concludes with recommendations for physiology educators as to how they can successfully develop and deliver remote laboratories.