Habib Bashour, Eva Smorodina, Matteo Pariset, Jahn Zhong, Rahmad Akbar, Maria Chernigovskaya, Khang Lê Quý, Igor Snapkow, Puneet Rawat, Konrad Krawczyk, Geir Kjetil Sandve, Jose Gutierrez-Marcos, Daniel Nakhaee-Zadeh Gutierrez, Jan Terje Andersen & Victor Greiff

Designing effective monoclonal antibody (mAb) therapeutics faces a multi-parameter optimization challenge known as “developability”, which reflects an antibody’s ability to progress through development stages based on its physicochemical properties. To chart natural and engineered DP landscapes, we computed 40 sequence- and 46 structure-based DPs of over two million native and human-engineered single-chain antibody sequences. We show that sequence DPs are more predictable than structure-based ones across different machine-learning tasks and embeddings, indicating a constrained sequence-based design space. Human-engineered antibodies localize within the developability and sequence landscapes of natural antibodies, suggesting that human-engineered antibodies explore mere subspaces of the natural one. Our work quantifies the plasticity of antibody developability, providing a fundamental resource for multi-parameter therapeutic mAb design.

Communications Biology July 2024

Eleanor L. Dearlove, David Chandler, Steve Edgington, Shaun D. Berry, Gareth Martin, Claus Svendsen & Helen Hesketh

Management of T. vaporariorum is problematic because of widespread pesticide resistance, and many greenhouse growers rely on biological control agents to regulate T. vaporariorum populations. However, these are often slow and vary in efficacy, leading to subsequent application of chemical insecticides when pest populations exceed threshold levels. In this study, we evaluated co-applications of the entomopathogenic fungi (EPF) Beauveria bassiana and Cordyceps farinosa and the chemical insecticide spiromesifen in laboratory bioassays. Results indicate the potential for combined applications of EPF and spiromesifen as an effective integrated pest management strategy and demonstrate the applicability of the MixTox model to describe complex mixture interactions.

Scientific Reports. July 2024

Nicole Pereira, Kathryn R. Hales, Andrew Mead, Lauren H. K. Chappell, Guy C. Barker, John P. Clarkson

In Europe, cavity spot disease continues to have a major impact on marketable yield. The lack of reliable inoculation methods for these Pythium pathogens has, for many years, hampered the identification of new effective crop protection products or carrot varieties that are resistant to the disease. In this research, inoculation methods were developed for P. violae using mycelium or oospores, each of which successfully induced typical cavity spot symptoms in both pot- and field-grown carrots as well as consistent root stunting in the former. These methods were also used to successfully identify carrot cultivars with resistance to cavity spot and confirmed the efficacy of the fungicide metalaxylM against the disease. Results therefore demonstrated that the inoculation methods should be reliable for identifying the efficacy of crop protection products, assessing cavity spot resistance and for further studies investigating the biology and epidemiology of the pathogen.

Plant Pathology. July 2024

Jing An, Rim Brik Chaouche, Leonardo I Pereyra-Bistraín, Hugo Zalzalé, Qingyi Wang, Ying Huang, Xiaoning He, Chloé Dias Lopes, Javier Antunez-Sanchez, Catherine Bergounioux, Claire Boulogne, Cynthia Dupas, Cynthia Gillet, José Manuel Pérez-Pérez, Olivier Mathieu, Nicolas Bouché, Sotirios Fragkostefanakis, Yijing Zhang, Shaojian Zheng, Martin Crespi, Magdy M Mahfouz, Federico Ariel, Jose Gutierrez-Marcos, Cécile Raynaud, David Latrasse, Moussa Benhamed

In recent years, the exploration of genome three-dimensional (3D) conformation has yielded profound insights into the regulation of gene expression and cellular functions in both animals and plants. Employing advanced high-throughput sequencing and microscopy techniques, we investigated the landscape of 26 histone modifications and RNA polymerase II distribution in tomato (Solanum lycopersicum). Our study unveiled a rich and nuanced epigenetic landscape, shedding light on distinct chromatin states associated with heterochromatin formation and gene silencing. Moreover, we elucidated the intricate interplay between these chromatin states and the overall topology of the genome. Employing a genetic approach, we delved into the role of the histone modification H3K9ac in genome topology. Notably, our investigation revealed that the ectopic deposition of this chromatin mark triggered a reorganization of the 3D chromatin structure, defining different TAD-like borders. Our work emphasizes the critical role of H3K9ac in shaping the topology of the tomato genome, providing valuable insights into the epigenetic landscape of this agriculturally significant crop species.

PNAS. July 2024

Mojgan Rabiey, Emily R. Grace, Paulina Pawlos, Muscab Bihi, Haleem Ahmed, Georgina E. Hampson, Amna Al Riyami, Leena Alharbi, Rosa Sanchez-Lucas, Naina Korotania, Maria Laura Ciusa, Olivia Mosley, Michelle T. Hulin, Laura Baxter, Sabrine Dhaouadi, Diana Vinchira-Villarraga, Robert W. Jacks

Pseudomonas syringae pathovar syringae (Pss) is a major pathogen of cherry (Prunus avium) causing bacterial canker of the stem, leaf and fruit, impacting productivity and leading to a loss of trees. In an attempt to find a treatment for this disease, naturally occurring bacteriophage (phage) that specifically target Pss is being investigated as a biocontrol strategy. However, before using them as a biocontrol treatment, it is important to both understand their efficacy in reducing the bacterial population and determine if the bacterial pathogens can evolve resistance to evade phage infection. To investigate this, killing curve assays of five MR phages targeting Pss showed that phage resistance rapidly emerges in vitro, even when using a cocktail of the five phages together. This study shows that understanding the genetic mechanisms of bacterial pathogen resistance to phages is important for helping to design a more effective approach to kill the bacteria while minimizing the opportunity for phage resistance to manifest.

Microbial Biotechnology. June 20204

Laura Reyes-Haro, Gillian Prince, Rommel Santiago Granja-Travez, David Chandler

The diamondback moth (DBM) (Plutella xylostella) causes large losses to global crop production. Conventional insecticides are losing effectiveness due to resistance. Consequently, there is a growing interest in sustainable control methods like entomopathogenic fungi (EPF) in Integrated Pest Management. However, the field efficacy of fungi varies due to environmental influences. In this study, a group of 50 Beauveria strains sourced from different locations were characterized by genotype and phenotype with respect to their conidial production, temperature and UV-B radiation tolerance, and virulence against DBM. Survival under environmental conditions is crucial for EPF-based commercial products against DBM. Results suggest strain tolerance to environmental stressors is more tied to specific micro-climatic factors than geographical origin. Each strain exhibited unique characteristics; for example, the most virulent strain (#29) was highly UV-sensitive. Therefore, characterizing diverse strains provides essential genotypic and phenotypic insights, which are fundamental for understanding their role as biocontrol agents while facilitating efficient biopesticide product development and uptake

Pest Management Science. June 2024