Biology subjects

Miller, S. C.

Publications and source records attributed to Miller, S. C..

4 recordsLinked to original sources

bioRxiv2026

Morphological shifts consistent with the island syndrome in land-bridge island birds

Land-bridge islands are former mainland areas isolated by post-glacial sea-level rise (<15,000 years) and the most common island type. Because of their recurrent connectivity with continents, it is unclear whether species on land-bridge islands can undergo evolutionary changes associated with the more isolated oceanic islands ( island syndrome). Here, we test the hypothesis that the selective environment on land-bridge islands exerts predictable and consistent evolutionary shifts in morphological traits of songbirds. We apply Bayesian hierarchical models to a morphological dataset of 6,917 individuals comprising 185 species of songbirds from four land-bridge islands (Bioko, Sri Lanka, Taiwan and Trinidad) and adjacent continents. Across all 185 species, we find that occurrence on a land-bridge island has clear directional effects on five morphological traits related to beak, wing, and tarsus, as well as a general increase in body size. At the species level, 57 out of 90 tested species exhibit significant morphological divergence between land-bridge island and mainland, yet for only 20 of these are the land-bridge island populations recognised as distinct endemic subspecies. Our results show that occurrence on land-bridge islands has a detectable effect on passerine morphology consistent with the island syndrome, and suggest these islands harbour previously unrecognized unique biodiversity.

evolutionary biology↗

bioRxiv2025

FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer

Despite the advancement in therapies, ovarian cancer treatment is challenging due to poor prognosis and high relapse associated with acquired resistance. Targeting overexpression of FOLR1 in ovarian cancers has proven to be an attractive strategy. The recent FDA approval of FOLR1 targeted antibody drug conjugate has shown promising results albeit resistance with repeated use appears inevitable. Emerging targeted alpha-particle therapies, particularly Actinium-225 (225Ac), for treating refractory cancers have opened avenues for improved therapeutic options. The success of alpha-particle therapy relies on tumor specific delivery of the alpha emitters. Herein we describe the first example of FOLR1-targeted 225Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal PET imaging demonstrated high tumor-specific uptake of FOLR1 in SKOV3 xenografts. FOLR1-targeted 225Ac demonstrated high therapeutic efficacy achieving marked tumor regression, 80% survival and 40% complete response. The therapy resulted in tumor specific double stranded DNA damage, and no obvious toxicity was observed in normal tissues. Estimated human dosimetry showed high absorbed dose for tumor and minimal absorbed dose for healthy tissues establishing its safety. In totality, FOLR1-targeted 225Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer.

bioengineering↗

bioRxiv2023

FruitFire: a luciferase based on a fruit fly metabolic enzyme

Firefly luciferase is homologous to fatty acyl-CoA synthetases from insects that are not bioluminescent. Here, we determined the crystal structure of the fruit fly fatty acyl-CoA synthetase CG6178 to 2.5 [A]. Based on this structure, we mutated a steric protrusion in the active site to create the artificial luciferase FruitFire, which prefers the synthetic luciferin CycLuc2 to D-luciferin by >1000-fold. FruitFire enabled in vivo bioluminescence imaging in the brains of mice using the pro-luciferin CycLuc2-amide. The conversion of a fruit fly enzyme into a luciferase capable of in vivo imaging underscores the potential for bioluminescence with a range of adenylating enzymes from nonluminescent organisms, and the possibilities for application-focused design of enzyme-substrate pairs.

biochemistry↗

bioRxiv2020

Methods for detecting PER2::LUCIFERASE bioluminescence rhythms in freely moving mice

Circadian rhythms are driven by daily oscillations of gene expression. An important tool for studying cellular and tissue rhythms is the use of a gene reporter, such as bioluminescence from the reporter gene luciferase controlled by a rhythmically expressed gene of interest. Here we describe methods that allow measurement of bioluminescence from a freely-moving mouse housed in a standard cage. Using a LumiCycle In Vivo (Actimetrics), we determined conditions that allow detection of circadian rhythms of bioluminescence from the PER2 reporter, PER2::LUC, in freely behaving mice. We tested delivery of D-luciferin via a subcutaneous minipump and in the drinking water. Further, we demonstrate that a synthetic luciferase substrate, CycLuc1, can support circadian rhythms of bioluminescence, even when delivered at a lower concentration than D-luciferin. We share our analysis scripts and suggestions for further improvements in this method. This approach will be straightforward to apply to mice with tissue-specific reporters, allowing insights into responses of specific peripheral clocks to perturbations such as environmental or pharmacological manipulations.

systems biology↗