Biology subjects

Nielsen, H. M.

Publications and source records attributed to Nielsen, H. M..

3 recordsLinked to original sources

bioRxiv2026

MORPHIS (MORPHological Interpretable Signature) captures heterogeneous treatment- and aging-related responses of single cells

Cell morphology encodes changes in cytoskeletal and organelle organization during disease, treatment, and aging, yet is often assessed qualitatively or through poorly interpretable feature sets extracted from microscopy images. Here we introduce MORPHIS (MORPHological Interpretable Signature), a machine learning framework on explainable, analytically rich features paired with statistical methodologies for robust and interpretable quantification of single-cell morphological signature. MORPHIS extracts compact, interpretable feature signatures that capture both perturbation-specific response magnitude and heterogeneous cellular responses. It accurately distinguishes treatment-specific morphological signatures of eight mechanistically distinct membrane-active and intracellular-targeting compounds in Caco-2 and HeLa cells elucidating conserved and divergent phenotypic responses among compound-classes, as well as ultrastructural nuclear alterations upon aging of C. elegans and quantifies heterogeneous single-cell fractional responses. By remaining cell-type and perturbation agnostic, MORPHIS provides a generalizable framework for quantifying morphological signatures across diverse biological contexts including pharmacological treatment or aging.

biophysics↗

bioRxiv2024

Controlled and polygynous mating in the black soldier fly: advancing breeding programs through quantitative genetic designs

In animal breeding programs, utilizing quantitative genetic designs such as the full-/half-sibling design is fundamental. A full-/half-sibling design demands that mating can be controlled, and individuals can be tracked, enabling construction of a pedigree. In nature, black soldier fly (Hermetia illucens (L.)) males are reported to gather in lekking groups to engage in competitive displays and courtship rituals before mating, and this lekking behavior is described as crucial for mating in this species. We show that a randomly chosen male and a randomly chosen virgin female can readily mate under LED lights in a small container at 28 {degrees}C and 70% RH, demonstrating the ability to mate selected pairs. For males given access to four females, all mated and the time until first mating was considerably shorter than for males given only one female, where 80% of the males mated. Furthermore, when adding four virgin females to a single male, males successfully mated all four females in 52% of cases within our four-hour trial, with 96% of males mating at least twice. Number of matings observed for a male correlated with the number of females from the container that laid an egg clutch, and almost all egg clutches produced offspring. Observed mating thus lead to fertilization, and consecutive matings were with new females resulting in full- and half-sibling offspring. Males with four females that mated a second female did so at a median time of less than three minutes upon ending previous mating, showing that polygynous mating occurred rapidly in this setup. Our findings pave the way for moving H. illucens breeding programs beyond mass selection towards advanced selective breeding designs where controlled mating is typically required. Such designs enable selection for multiple traits simultaneously while controlling inbreeding and can drastically increase rates of selection responses compared to mass selection.

animal behavior and cognition↗

bioRxiv2021

Polysorbate 80 Controls Morphology, Structure and Stability of Human Insulin Amyloid-Like Spherulites

Amyloid protein aggregates are not only associated with neurodegenerative diseases and may also occur as unwanted by-products in protein-based therapeutics. Surfactants are often employed to stabilize protein formulations and reduce the risk of aggregation. However, surfactants alter protein-protein interactions and may thus modulate the physicochemical characteristics of any aggregates formed. Human insulin aggregation was induced at low pH in the presence of varying concentrations of the surfactant polysorbate 80. Various spectroscopic and imaging methods were used to study the aggregation kinetics, as well as structure and morphology of the formed aggregates. Molecular dynamics simulations were employed to investigate the initial interaction between the surfactant and insulin. Addition of polysorbate 80 slowed down, but did not prevent, aggregation of insulin. Amyloid spherulites formed under all conditions, with a higher content of intermolecular beta-sheets in the presence of the surfactant above its critical micelle concentration. In addition, a denser packing was observed, leading to a more stable aggregate. Molecular dynamics simulations suggested a tendency for insulin to form dimers in the presence of the surfactant, indicating a change in protein-protein interactions. It is thus shown that surfactants not only alter aggregation kinetics, but also affect physicochemical properties of any aggregates formed.

biophysics↗