Biology subjects

Fellows, B.

Publications and source records attributed to Fellows, B..

3 recordsLinked to original sources

bioRxiv2026

Phenotypic plasticity as a route to population shifts via tipping points

Environmental change has caused dramatic global declines in biodiversity, with some species showing abrupt and often irreversible changes in population abundance. These regime shifts can occur when environmental thresholds, known as tipping points, are passed. Many species can respond to environmental change via phenotypic plasticity with the expectation that strong phenotypic plasticity reduces the risk of regime shifts by enabling a species to rapidly respond to environmental change, potentially mitigating the risks of population collapse. Testing the theory that phenotypic plasticity buffers against regime shifts requires a novel whole population approach that robustly considers the feedback mechanisms between environment, phenotype and population density, common to the life-history of many species. For this purpose we develop a tractable mathematical framework, and demonstrate, counter-intuitively, that phenotypic plasticity can induce tipping points, due to the inclusion of feedback mechanisms that operate at both the level of the organism and population. Consequently, predicting the existence of potentially devastating tipping points and so understanding ecosystem collapse is more nuanced than current thinking suggests.

ecology↗

bioRxiv2025

Magnetic Particle Imaging Lymphography (MPIL): A novel technique for lymph node mapping

During metastasis, tumour cells drain to nearby lymph nodes, the first of which are named the sentinel lymph node(s) (SLN). SLN biopsy (SLNB) determines if metastasis has occurred. Traditionally, SLNB involves injecting a Technetium-labeled tracer peritumourally, pre-operative imaging with SPECT to locate the SLN, and surgery guided by a gamma probe to remove them. Limitations include short tracer half-life which can make scheduling the SLNB difficult, and radiation dose to patients and healthcare workers. Alternatively, magnetic localization, with superparamagnetic iron oxide nanoparticles (SPIONs) as the tracer and a magnetometer to detect SPIONs in the SLN during surgery can be used, however, this lacks pre-operative imaging. Magnetic Particle Imaging (MPI) is a new imaging modality that directly detects SPIONs, holding potential for pre-operative imaging in magnetic SLNB. SPIONs for SLNB should have rapid drainage, high SLN accumulation, and high specificity to the SLN. For MPI Lymphography (MPIL), high particle sensitivity is also important. This study assesses the in vivo pharmacokinetics for SLN mapping with MPIL in a murine model, using five commercially available SPIONs of varying iron core sizes and surface coatings. We show that some SPIONs provide higher MPI signal at the SLN and show the potential to detect higher echelon nodes (HENs). PEGylation of SPIONs and mannose targeted SPIONs increase clearance from the injection site and the mannose targeted SPION reduces flow to HENs.

biophysics↗

bioRxiv2024

Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

IntroductionClinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. MethodsHuman-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co- incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 106) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc. ResultsNK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 107 labeled NK-92 cells was demonstrated on clinical-scale MPI. ConclusionMPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.

biophysics↗