Morales, J. A. | bioRxiv Science

bioRxiv2026

Biochemical Logic Computation Through Repurposing Natural bZIP Protein Interaction Networks

Competitive protein dimerization networks offer an alternative to transcriptional genetic circuits by enabling fast molecular decision-making through direct protein-protein interactions. Implementing these networks currently requires challenging de novo protein design. In this work, we circumvent this limitation by repurposing natural, experimentally pre-characterized basic leucine zipper (bZIP) transcription factor networks. By keeping natural binding affinities and modulating only component monomer concentrations via a customized genetic algorithm, we comprehensively evaluate the computational versatility and robustness of these natural substrates. We identified 135 individual networks capable of implementing Boolean logic, with the most versatile natural clusters computing up to 15 of the 16 possible two-input logic gates, including the non-linearly separable XOR and XNOR. Computational versatility increased with network size and connectivity, and robustness analysis revealed that many optimized networks preserved reliable logical behavior despite substantial stochastic expression noise. These results demonstrate that natural bZIP networks possess substantial latent computational capacity and can perform reliable biochemical computation through concentration tuning alone, providing a realistic foundation for developing scalable protein-based biocomputing platforms for future synthetic biology applications.

synthetic biology↗

bioRxiv2022

Boid Inclusion Body Disease (BIBD) Is Also a Disease of Wild Boa Constrictors

Reptarenaviruses cause Boid Inclusion Body Disease (BIBD), a potentially fatal disease, occurring in captive constrictor snakes boas and pythons worldwide. Classical BIBD, characterized by the formation of pathognomonic cytoplasmic inclusion bodies (IBs), occurs mainly in boas, whereas in pythons, for example, reptarenavirus infection most often manifests as central nervous system signs with limited IB formation. The natural hosts of reptarenaviruses are unknown, although wild constrictor snakes are among the suspects. Here, we report BIBD with reptarenavirus infection in indigenous captive and wild boid snakes in Costa Rica using histology, immunohistology, transmission electron microscopy, next-generation sequencing (NGS), and RT-PCR. The snakes studied represented diagnostic post mortem cases of captive and wild caught snakes since 1989. The results from NGS on archival paraffin blocks confirm that reptarenaviruses have been present in wild boa constrictors in Costa Rica already in the 1980s. Continuous sequences de novo assembled from the low-quality RNA obtained from paraffin embedded tissue allowed the identification of a distinct pair of reptrarenavirus S and L segments in all studied animals; in most cases reference assembly could recover almost complete segments. Sampling of three prospective cases in 2018 allowed examination of fresh blood or tissues, and resulted in identification of additional reptarenavirus segments and hartmanivirus co-infection. Our results show that BIBD is not only a disease of captive snakes, but also occurs in indigenous wild constrictor snakes in Costa Rica, suggesting boa constrictors to play a role in natural reptarenavirus circulation. IMPORTANCEThe literature describes cases of boid inclusion body disease (BIBD) in captive snakes since the 1970s, and in the 2010s, others and we identified reptarenaviruses as the causative agent. BIBD affects captive snakes globally, but the origin and the natural host of reptarenaviruses remains unknown. In this report, we show BIBD and reptarenavirus infections in two native Costa Rican constrictor snake species, and by studying archival samples, we show that both the viruses and the disease have been present in wild snakes in Costa Rica at least since the 1980s. The diagnosis of BIBD in wild boa constrictors suggests that this species plays a role in the circulation of reptarenaviruses. Additional sample collection and analysis would help to clarify this role further and the possibility of e.g. vector transmission from an arthropod host.

microbiology↗