Biology subjects

Bryant, K.

Publications and source records attributed to Bryant, K..

6 recordsLinked to original sources

bioRxiv2025

A Comprehensive Mathematical Model Simulating the Adaptive Immune Response

Adaptive immunity plays a crucial role in defending against invading pathogenic microorganisms. It encompasses both humoral and cellular immune responses. For the first time, we have systematically developed a mathematical model of adaptive immunity that comprehensively incorporates the effects of both humoral and cellular immunity. Our model successfully explains several key immunological phenomena, including the formation of immune memory (involving both B-cell and T-cell memory), the mechanism of original antigenic sin, the basis of secondary infections, and the processes of activation and exhaustion in cellular immunity. Furthermore, we employed a discrete time-scale agent-based modeling approach to simulate the dynamics of the adaptive immune response following pathogen invasion, with a specific focus on elucidating the mechanisms underlying chronic infection. Finally, we have established a novel mathematical model of the interaction between cancer cells and the immune system, providing a more robust theoretical foundation for cancer immunotherapy.

immunology↗

bioRxiv2025

The genomic complexity of invasion: cryptic lineages, founder effects, and polygenic sex determination in armored catfish

Genetic biocontrol approaches offer promising tools for managing invasive species. However, their success depends on species identity, demographic history, and the genomic architecture of sex determination, which remain poorly resolved for many non-model taxa. We integrated high-quality genome assembly, whole-genome resequencing, and population genomics to evaluate biocontrol feasibility in invasive suckermouth armored catfish (Loricariidae) in Texas. Mitochondrial phylogenies and genome-wide SNPs revealed cryptic diversity, with distinct lineages from at least two genera (Hypostomus and Pterygoplichthys) exhibiting strong drainage-level genetic differentiation. Effective population size estimates were exceptionally low, consistent with founder effects and moderate inbreeding. Genome-wide association analyses detected no large-effect loci for sex in either genus, despite high statistical power in Hypostomus, suggesting that sex determination is polygenic and/or environmentally influenced. These results identify key biological constraints for sex-ratio-based biocontrol and underscore the importance of genomic assessments prior to management interventions. More broadly, our study highlights how integrating genomic resources, demographic inference, and evolutionary context can guide invasive species control strategies.

genetics↗

bioRxiv2025

Cross-species Standardised Cortico-Subcortical Tractography

Despite their importance for brain function, cortico-subcortical white matter tracts are underrepresented in diffusion MRI tractography studies. Their non-invasive mapping is more challenging and less explored compared to other major cortico-cortical bundles. We introduce a set of standardised tractography protocols for delineating tracts between the cortex and various deep subcortical structures, including the caudate, putamen, amygdala, thalamus and hippocampus. To enable comparative studies, our protocols are designed for both human and macaque brains. We demonstrate how tractography reconstructions follow topographical principles obtained from tracers in the macaque and how these translate to humans. We show that the proposed protocols are robust against data quality and preserve aspects of individual variability stemming from family structure in humans. Lastly, we demonstrate the value of these species-matched protocols in mapping homologous grey matter regions in humans and macaques, both in cortex and subcortex.

neuroscience↗

bioRxiv2024

PTPN11 Mutation Clonal Hierarchy in Acute Myeloid Leukemia

Mutations in protein tyrosine phosphatase non-receptor type 11 (PTPN11) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny of PTPN11 mutations, we utilized single-cell DNA sequencing and identified that PTPN11 mutations can occur as initiating events in some AML patients when accompanied by strong oncogenic drivers, commonly NPM1 mutations. The co-driver role of PTPN11 mutations was confirmed in a novel murine model that exhibits an AML phenotype with early expansion of a diverse set of variably differentiated myeloid cells that engrafted into immunodeficient and immunocompetent mice. This immune diversity was reconstituted from early precursor cells when engrafted into immunodeficient mice. Moreover, immune diversity was also observed in the blast component of patient samples with NPM1 and PTPN11 mutations, providing novel antigen targets for immune based approaches in this subset of AML that is resistant to multiple targeted therapies.

cancer biology↗

bioRxiv2024

Dynamic Modeling of Antibody Repertoire Reshaping in Response to Viral Infections

For many years, researchers have emphasized the production of high-affinity specific antibodies by hosts during viral infections. However, this has made it challenging for immunologists to systematically evaluate the initiation mechanisms of humoral immunity in specific immune responses. Employing mathematical modeling, we have systematically investigated the dynamic changes of the entire antibody atlas in response to exogenous antigenic stimuli, including viral infections. Our study reveals that the hosts antibody atlas is reshaped during viral infection, not through the proliferation of individual antibody types, but rather through the proliferation of antibody pools with strong binding activity. Moreover, we observe a contraction in pools of antibodies with low binding activity. We have identified the crucial role of self-antigens in maintaining antibody persistence, which can effectively explain the organisms lifelong protection against pathogens that are less prone to mutation. Using this model, we further explore the mechanisms underlying original antigenic sin and elucidate the specific practical applications of this model. This research transcends the limitations of mere mathematical parameter fitting, as we endeavor to elucidate the complex humoral immune processes using physical mechanisms as a foundation. Our work contributes to a renewed understanding of the antibody elicitation process in specific immune responses.

immunology↗

bioRxiv2023

Multifunctional Materials Strategies for Enhanced Safety of Wireless, Skin-Interfaced Bioelectronic Devices

Many recently developed classes of wireless, skin-interfaced bioelectronic devices rely on conventional thermoset silicone elastomer materials, such as poly(dimethylsiloxane) (PDMS), as soft encapsulating structures around collections of electronic components, radio frequency antennas and, commonly, rechargeable batteries. In optimized layouts and device designs, these materials provide attractive features, most prominently in their gentle, noninvasive interfaces to the skin even at regions of high curvature and large natural deformations. Past work, however, overlooks opportunities for developing variants of these materials for multimodal means to enhance the safety of the devices against failure modes that range from mechanical damage to thermal runaway. This paper presents a self-healing PDMS dynamic covalent matrix embedded with chemistries that provide thermochromism, mechanochromism, strain-adaptive stiffening, and thermal insulation, as a collection of attributes relevant to safety. Demonstrations of this materials system and associated encapsulation strategy involve a wireless, skin-interfaced device that captures mechanoacoustic signatures of health status. The concepts introduced here can apply immediately to many other related bioelectronic devices.

bioengineering↗