Patrick Michael Sexton

Structural basis of MK-97 positive allosteric modulation at the M4 mAChR

This paper reports the cryo-EM structure of the M4 mAChR bound to MK-97 and acetylcholine, revealing how MK-97's binding mode improves PAM activity through distributed interactions.

In vivo functional profiling and structural characterisation of the human Glp1r A316T variant

This study investigates the human Glp1r A316T variant's effects on glucose metabolism and GLP-1RA responses using mouse models and structural analyses.

Design of peptide-based PAC1 antagonists combining molecular dynamics simulations and a biologically relevant cell-based assay

The paper designs peptide-based PAC1 antagonists using molecular dynamics simulations and a cell-based assay, finding that some proposed small molecule antagonists lack activity while confirming the efficacy of PACAP(6-38) and M65.

A Versatile Antibody Capture System that Drives Precise In Vivo Delivery of mRNA loaded Lipid Nanoparticles and Enhances Gene Expression

This paper introduces an antibody capture system for LNPs that enhances mRNA delivery and gene expression by enabling precise targeting to T cells with minimal off-target effects.

Prolonged signaling of backbone-modified glucagon-like peptide-1 analogues with diverse receptor trafficking

This study identifies GLP-1 analogues with prolonged signaling by modifying specific amino acids, showing how receptor trafficking and peptide structure affect signaling duration.

De novo design of miniprotein agonists and antagonists targeting G protein-coupled receptors

This paper presents computational methods for designing GPCR-binding miniproteins and validates them through high-throughput screening, producing agonists and antagonists for multiple GPCRs.

Activation of M1 muscarinic receptors reduce pathology and slow progression of neurodegenerative disease.

This study shows that activating M1 muscarinic receptors with VU846 slows murine prion disease progression, reduces neuroinflammation, and preserves synaptic proteins.

Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification

This study performs a GWAS on random glucose measurements in 493,036 individuals, identifying 128 loci associated with glycaemic traits and providing insights into diabetes biology and treatment.