Biology subjects

Suderman, R.

Publications and source records attributed to Suderman, R..

3 recordsLinked to original sources

bioRxiv2023

nanoCLAMP potently neutralizes SARS-CoV-2 and protects K18-hACE2 mice from infection

Intranasal treatments, combined with vaccination, has the potential to slow mutational evolution of virusues by reducing transmission and replication. Here we illustrate the development of a SARS-CoV-2 receptor binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope binding nanoCLAMP, P2609. The resulting multimerised nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B.1.351) RBD (KD < 1 pM), and decreasing affinity for the Delta (B.1.617.2) and Omicron (B.1.1.529) variants (86 pM and 19.7 nM, respectively). P2712 potently inhibited ACE2:RBD interaction, suggesting its utility as a therapeutic. With an IC50 = 0.4 {+/-} 0.1 nM obtained from neutralization experiments using pseudoviral particles as well as patient cultured SARS-CoV-2 samples, nanoCLAMP P2712 protected K18-hACE2 mice from SARS-CoV-2 infection, reduced viral loads in the lungs and brains, and reduced associated upregulation of inflammatory cytokines and chemokines. Together, our findings warrant further investigation into the development of nanoCLAMPs as effective intranasally delivered COVID19 therapeutics.

bioengineering↗

bioRxiv2017

TRuML: A Translator for Rule-Based Modeling Languages

Rule-based modeling languages, such as the Kappa and BioNetGen languages (BNGL), are powerful frameworks for modeling the dynamics of complex biochemical reaction networks. Each language is distributed with a distinct software suite and modelers may wish to take advantage of both toolsets. This paper introduces a practical application called TRuML that translates models written in either Kappa or BNGL into the other language. While similar in many respects, key differences between the two languages makes translation sufficiently complex that automation becomes a useful tool. TRuML accommodates the languages complexities and produces a semantically equivalent model in the alternate language of the input model when possible and an approximate model in certain other cases. Here, we discuss a number of these complexities and provide examples of equivalent models in both Kappa and BNGL.\n\nCCS CONCEPTS* Applied computing [->] Systems biology; * Computing methodologies [->] Simulation languages;

systems biology↗

bioRxiv2017

Understanding the dynamics of scaffold-mediated signaling

Many signaling networks involve scaffold proteins that bind multiple kinases in kinase cascades. While scaffolds play a fundamental role in regulating signaling, few hypotheses regarding their function have been rigorously examined. Here, we used dynamical models of scaffold signaling to investigate the impact scaffolds have on network behavior. We considered two paradigms of scaffold assembly: as either the nucleation point for assembly of discrete multi-subunit proteins (the machine paradigm) or a platform upon which kinases independently associate (the ensemble paradigm). We found that several well-accepted hypotheses regarding the role of scaffolds in regulating signal response either do not hold or depend critically on the assembly paradigm employed. In addition to providing novel insights into the function of scaffold proteins, our work suggests experiments that could distinguish between assembly paradigms. Our findings should also inform attempts to target scaffold proteins for therapeutic intervention and the design of scaffolds for synthetic biology.

systems biology↗