Biology subjects

Herbst, C.

Publications and source records attributed to Herbst, C..

3 recordsLinked to original sources

bioRxiv2025

A conserved fungal transcription factor domain drives protein-protein interactions and necrotrophic effector-mediated virulence in Parastagonospora nodorum

The fungal pathogen Parastagonospora nodorum utilises necrotrophic effectors (NEs) to cause chlorosis and necrosis on wheat. NE expression is mediated by an assortment of transcription factors (TF), the most well-characterised of which is PnPf2. Orthologues of PnPf2 regulate virulence in phytopathogenic fungi across the Ascomycete fungal lineage, yet their protein architecture remains functionally uncharacterised. These orthologues are characterised by the archetypal N-terminal Zn2Cys6 zinc-finger DNA-binding domain (DBD), a conserved yet poorly characterised middle-homology region (MHR) and a C-terminal disordered region. We investigated the role of each of the three domains through PnPf2 truncation mutants in situ. This revealed the conserved MHR of PnPf2 is required for the development of disease symptoms on wheat, but also that the C-terminal disordered region in-part modulates NE expression. Domain-interaction analysis through yeast-2-hybrid (Y2H) screening reveals PnPf2 forms a homodimer mediated by the MHR, indicating its importance mediating protein-protein interactions. Using the MHR as a bait in library-scale protein-protein interaction Y2H assays, we identified the COP9-signalosome protein PnCsn6 as a key interaction partner. PnCsn6 is essential for disease symptoms during P. nodorum infection on wheat, including NE expression. Our study presents the first domain-level functional investigation this virulence-regulating TF orthologue, the results of which underpin the essential role of the MHR in driving protein-protein interactions and effector regulation. It also reveals an essential protein-signalling pathway with which PnPf2 directly interacts and shares regulatory control of virulence.

molecular biology↗

bioRxiv2021

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses

Nucleoside modified mRNA combined with Acuitas Therapeutics lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses. In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.

immunology↗

bioRxiv2021

How to attract and retain health workers in rural areas of a fragile state: findings from a labour market survey in Guinea

Most countries face challenges attracting and retaining health staff in remote areas but this is especially acute in fragile and shock-prone contexts, like Guinea, where imbalances in staffing are high and financial and governance arrangements to address rural shortfalls are weak. The objective of this study was to understand how health staff could be better motivated to work and remain in rural, under-served areas in Guinea. In order to inform the policy dialogue on strengthening human resources for health, we conducted three nationally representative cross-sectional surveys, adapted from tools used in other fragile contexts. We found that the locational job preferences of health workers in Guinea are particularly influenced by opportunities for training, working conditions, and housing. Most staff are satisfied with their work and with supervision, however, financial aspects and working conditions are considered least satisfactory, and worrying findings include the high proportion of staff favouring emigration, their high tolerance of informal user payments, as well as their limited exposure to rural areas during training. Based on our findings, we highlight measures which could improve rural recruitment and retention in Guinea and similar settings. These include offering upgrading and specialization in return for rural service; providing greater exposure to rural areas during training; increasing recruitment from rural areas; experimenting with fixed term contracts in rural areas; and improving working conditions in rural posts. The development of incentive packages should be accompanied by action to tackle wider issues, such as reforms to training and staff management.

scientific communication and education↗