Publications

Kristine Arnvig’s group published paper in Nucleic Acids Research Journal

Kristine Arnvig’s group published paper in Nucleic Acids Research Journal

Kristine Arnvig’s research group recently published a paper in the Nucleic Acids Journal. Full paper can be accessed here (doi.org/10.1093/nar/gkae338) .

Unexpected complexity of vitamin B12-sensing RNA elements in Mycobacterium tuberculosis.

The bacterium Mycobacterium tuberculosis (Mtb) lacks the ability to produce vitamin B12, yet this co-factor plays a significant role in Mtb’s metabolism and gene regulation. Research conducted by Tine Arnvig’s team reveals an intriguing additional layer of control exerted by vitamin B12-sensing RNA elements, known as riboswitches, over metabolic and virulence genes in this pathogen. Beyond uncovering the B12-dependent inhibition of translation initiation, the team also uncovered two novel translated uORFs, which influence riboswitch regulation. In one instance, they identified a crucial translational link between the uORF and its downstream gene, facilitating translation re-initiation independently of Shine-Dalgarno sequences, alongside stop codon suppression, resulting in the synthesis of a frameshifted fusion protein. Essentially, Mtb demonstrates the capacity to generate similar proteins with differing N-termini, akin to eukaryotic alternative splicing. Lead author Dr. Terry Kipkorir remarks, “[This] represents yet another example of how Mtb breaks the mould in our understanding of gene expression control.’

Posted by Cyndy Thooi in Publications
Prof Finn Werner’s group published paper in Nature Communications – Idiosyncratic chromatin regulates adaptive immunity in archaea at the level of transcription

Prof Finn Werner’s group published paper in Nature Communications – Idiosyncratic chromatin regulates adaptive immunity in archaea at the level of transcription

The prevalent state of DNA in all cells is chromatin that is made of protein-DNA complexes which are dynamic, complex and heterogenous. The exact composition of the chromatin determines its properties, how it regulates transcription and genome architecture. A breakthrough article by the RNAP laboratory at UCL published today in the journal Nature Communications describes how two chromatin proteins, Cbp1 and Cren7, collaborate to modulate gene regulation in opposing ways. While this type of specialised chromatin stimulates the expression of long crRNA arrays that facilitate adaptive immunity in archaea (‘CRISPR’), it cryptic promoters that frequently reside in the memory of the ‘immunity’ system, in the ‘CRISPR spacers’. This transcription interference by cryptic promoters limits how much spacer information can be stored in CRISPR arrays, or worse lead the malfunction of the system. Dr. Fabian Blombach from the ISMB RNAP laboratory, the lead author of the study, says ‘There is a lot of attention in the field to histones and their role in gene regulation, but we can learn so much from archaeal and bacterial chromatin proteins, including some of the ground rules that shape the interaction between chromatin proteins and transcription in all cellular life.’

Sulfolobus Cbp1 and Cren7 form chimeric chromatin structures on large archaeal CRISPR arrays. Cbp1 confers sequence-specificity and interacts via its HTH3 domain interactions with Cren7. Together, they enhance leader promoters but repress CRISPR spacer-encoded cryptic promoters1. Archaea research in the RNAP lab is funded by the Wellcome Trust Investigator in Science Award (WT207446/Z/17/Z).

References

  1. Blombach, F., Sykora, M., Case, J., Feng, X., Baquero, D.P., Fouqueau, T., Phung, D.K., Barker, D., Krupovic, M., She, Q., and Werner, F. (2024). Cbp1 and Cren7 form chromatin-like structures that ensure efficient transcription of long CRISPR arrays. Nat Commun 15, 1620. 10.1038/s41467-024-45728-8.

Full paper can be read here.

Posted by Cyndy Thooi in Publications
Kostas Thalassinos’ group published paper in Molecular & Cellular Proteomics (MCP) online

Kostas Thalassinos’ group published paper in Molecular & Cellular Proteomics (MCP) online

Together with the Topf lab at the Centre for Structural Systems Biology (Hamburg), Kish Adoni from the Thalassinos lab has developed a novel pipeline that incorporates crosslinking-mass spectrometry data into AlphaFold2 for improved accuracy of protein structure determination. They found this workflow to be of particular relevance to proteins that occupy multiple conformations. The function of a protein is determined by its structure, via the structure-function relationship, and thousands of proteins modify their shape upon external cues such as molecular or protein interactions. As such, probing these conformational modifications is pivotal to characterising the protein’s behaviour, for example in the context of drug design when developing pharmaceuticals for drug-protein interactions.

Full paper can be read here.

Posted by Cyndy Thooi in Publications
Franca Fraternali’s group published paper in Nature Methods

Franca Fraternali’s group published paper in Nature Methods

Dr Joseph Ng and Prof. Franca Fraternali have published the novel method sciCSR to analyse CSR (class-switch recombination) and the antibody response by using molecular data from single B-cells (Nature Methods)

sciCSR allows researchers to analyse in high detail how CSR occurs across time. By building mathematical models to infer CSR events probabilistically, sciCSR can be applied in scenarios including vaccination and gene knockouts and to predict how antibody responses are mounted against immune challenges.

Posted by Cyndy Thooi in Publications
Professor Helen Saibil’s group published papers in The Nature Communications, The EMBO Journal and Nature Chemical Biology

Professor Helen Saibil’s group published papers in The Nature Communications, The EMBO Journal and Nature Chemical Biology

Professor Helen Saibil’s research group published a paper titled ‘Structural journey of an insecticidal protein against western corn rootworm’ in Nature Communications on 13 July 2023. The full paper is available here.

Her group published two other papers recently, the paper titled ‘Structural basis of ubiquitin-independent PP1 complex disassembly by p97’ was published in The EMBO Journal on 2 June 2023. The full paper is available here.

Finally, a paper on ‘A structural basis for prion strain diversity’ was published in the Nature Chemical Biology on 16 January 2023. The full paper is available here.

Posted by Cyndy Thooi in Publications
Trainspotting within the cell’s antenna

Trainspotting within the cell’s antenna

New research, published in Cell, illuminates the molecular “trains” that transport cargoes essential for human health and development.

Virtually every cell in the human body grows an antenna-like structure on its surface, which is used to receive vital signals from the body and the outside world. Perturbations in this process cause a wide range of human disorders spanning loss of eyesight, cystic kidneys, breathing problems, and infertility, among other conditions.

New research from the Institute of Structural and Molecular Biology has shed new light on the molecular “trains” that underpin this process, and how they misfunction in disease. Using cryo-election microscopy, a powerful technique for determining the three-dimensional shape of biological molecules, the team was able to see the structure of the proteins that make up the trains and how they carry their vital cargoes. Cell biology experiments showed that the range of cargoes transported by the trains is even wider than anticipated. The findings will help researchers to interpret patient mutations in the proteins that cause disease and design new experiments.

This research, funded by the Wellcome Trust and BBSRC with co-first authors Dr. Sophie Hesketh and Dr. Aakash Mukhopadhyay and co-senior authors Dr. Katerina Toropova and Dr. Anthony Roberts, was published in Cell on 2 December 2022: https://www.cell.com/cell/fulltext/S0092-8674(22)01422-2

Posted by ubcg03u in Achievements, News, Publications
The killer weapon of the immune system

The killer weapon of the immune system

Researchers in Biological Sciences at Birkbeck, in collaboration with a group at the Peter MacCallum Cancer Centre in Melbourne, have determined the structure of a protein assembly used by the immune system to kill unwanted cells. The immune system uses cytotoxic T lymphocytes and natural killer cells to act as executioners when it detects the presence of virally infected or cancerous cells.  The cytotoxic and killer cells contain small membrane parcels filled with the protein perforin, which can punch holes through cell membranes, along with the toxic granzyme enzymes. When an infected cell is detected, the killer cell latches onto it and ejects some of the membrane parcels with their toxic contents so that the perforin protein punches holes in the target cell membrane, through which the toxic granzymes enter, rapidly causing the target cell to die (Figure 1). The cytotoxic and killer cells are professional assassins that can kill many victims in rapid succession, briefly attaching, ejecting their lethal cargo, and then moving on to the next victim. Perforin is an essential protein for survival, and unfortunate individuals who lack functional perforin usually die of infection or cancer in early childhood. On the other hand, over active killer cells can also cause serious damage, by triggering inflammation and killing healthy cells.

A former postdoctoral researcher, Marina Ivanova (now at Imperial College), determined the perforin structure in the group of Professor Helen Saibil, and the paper has been published in Science Advances. Perforin is made as single protein molecules that are stored inside their membrane compartment until they are needed, but when they are released, they join up into rings of around 22 molecules and undergo a dramatic shape change in order to punch the hole through the target membrane. Two parts of the protein that are at first coiled up in the molecule extend and join up into the ring to punch through the membrane. This shape change is shown in Figure 2, with the part of the protein that makes the big change highlighted in pink.

Figure 3 shows two views of a perforin ring (multicoloured molecules) enclosing a hole in a cell membrane (shown as a pale blue slab). Now that we know the details of the pore structure, it will be possible to think about designing drugs to either enhance or prevent its activity. This could eventually lead to new therapeutics for certain autoimmune diseases and the condition familial hemophagocytic lymphohistiocytosis.

Ivanova, M.E., Lukoyanova, N., Malhotra, S., Topf, M., Trapani, J.A., Voskoboinik, I., Saibil, H.R. (2022) The pore conformation of lymphocyte perforin. Science Advances 8, eabk3147.

Posted by ubcg03u in News, Publications