Biology subjects

Bradlaugh, A. A.

Publications and source records attributed to Bradlaugh, A. A..

3 recordsLinked to original sources

bioRxiv2025

How the Drosophila Cryptochrome C-terminus mediates magnetosensitivity

The Earths magnetic field plays an important role in the seasonal migrations of many species of animals. A Cryptochrome (CRY)-based radical pair mechanism (RPM) has been suggested to underlie the mechanistic basis of animal magnetosensitivity and navigation. The quantum spin state of a radical pair involving flavin adenine dinucleotide (FAD) bound to CRY in the canonical pocket is sensitive to external magnetic fields that can alter the signalling concentration of activated CRY1-5. However, several experimental observations challenge this model including the finding that the C-terminal fragment of Drosophila CRY (DmCRY), which lacks any canonical FAD binding pocket, and human CRY2, which lacks affinity for FAD, are sufficient to support magnetosensitivity6-9. Here, we use all-atom molecular dynamic (MD) simulations, alongside in vitro and in vivo analyses to reveal that the C-terminus of Drosophila CRY (DmCRY-CT) binds FAD. FAD binding is required for transduction of a magnetic signal within cells, and, in vitro, initiates formation of high molecular weight DmCRY-CT oligomers, including large insoluble aggregates reminiscent of CRY photobodies observed in plants10-14. These results provide a plausible mechanistic basis for several experimental observations that have reported non-canonical magnetosensitivity in animals.

biochemistry↗

bioRxiv2025

Circadian Rhythms Time Seizure Severity in Drosophila

It is established that epilepsy patients can exhibit 24-hour rhythms in seizure severity and occurrence. While the pathways underlying seizure rhythmicity remain poorly understood, it seems likely that a contribution from the biological clock is involved. A better understanding of any such contribution may translate to better treatments. Here, the influence of the 24 h circadian rhythm on seizure activity in Drosophila melanogaster is investigated. Seizure-susceptible bang-sensitive julius seizure (jus) mutants were subjected to mechanically induced seizure at six different zeitgeber points. A clear sex- dependent phenotype was observed, with seizure severity showing a greater time-of-day effect in females, than males. The temporal pattern of seizure recovery time was bimodal, exhibiting both a morning and an evening peak. Rearing flies in constant light, which renders the molecular clock dysfunctional, abolished the seizure rhythm. Conversely, female seizure mutants reared in constant darkness, allowing free running of the circadian clock, continued to exhibit a bimodal rhythm of seizure severity. These findings support a role for the biological clock in seizure activity, at least in female Drosophila. Thus, this study validates Drosophila as a potential model for the identification of mechanisms modulating seizure rhythmicity, with the potential to aid future treatment of epilepsy.

neuroscience↗

bioRxiv2024

Circadian control in the timing of critical periods during Drosophila larval neuronal development.

Critical periods (CPs) of development are temporal windows of heightened neural plasticity. Activity perturbation during CPs can produce significant, and permanent, alterations to the development of neural circuits. In this study we report a circadian mechanism underlying the timing of CPs in Drosophila embryonic and larval development. These CPs occur at [~]24 hr intervals and are open to manipulation through blue light (BL)-activation of the circadian regulator Cryptochrome (CRY). This manipulation is sufficient to destabilize the larval CNS, evidenced by an induced seizure phenotype when tested at third instar (L3). In addition to CRY nulls, genetic ablation of the period gene also mitigates the BL exposure seizure phenotype and, moreover, alleles of period that affect circadian timing alter the timing of the CPs. Our analysis shows a clear role for the main clock neuropeptide, pigment dispersing factor (PDF), to transduce the output of these CPs. Targeted PDF receptor knockdown, in either GABAergic or CRY-positive neurons, is sufficient to prevent the CRY-mediated seizure phenotype. This study is a first demonstration of a circadian mechanism in Drosophila larvae, and whilst this alone is of major significance, our results highlight the potential of using Drosophila larvae as a model to investigate the impact of circadian rhythms on early neuronal development in higher organisms, which remains experimentally challenging. Significance StatementWhilst the role of the biological clock is well understood in adult organisms, the same is not true for embryonic development. How the maternal clock impacts the mammalian fetus remains poorly understood. Given that many expectant mothers experience altered circadian rhythms, largely due to nightshift working, it is important to address these concerns. Here we identify clock-mediated periods in neural development of the embryonic Drosophila which can be manipulated by light. These findings provide an experimental opportunity to better understand the role of the circadian clock in early development.

neuroscience↗