Biology subjects

Griffin, G.

Publications and source records attributed to Griffin, G..

2 recordsLinked to original sources

bioRxiv2023

Human Plasma Proteomic Profile of Clonal Hematopoiesis

Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer novel insights into downstream clinical consequences. Here, we explore such patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 ancestrally diverse participants (3,881 with CHIP) from NHLBI TOPMed and UK Biobank with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2,917 proteins by Olink in UK Biobank), we identified 32 and 345 unique proteins from TOPMed and UK Biobank, respectively, associated with the most prevalent driver genes (DNMT3A, TET2, and ASXL1). These associations showed substantial heterogeneity by driver genes, sex, and race, and were enriched for immune response and inflammation pathways. Mendelian randomization in humans, coupled with ELISA in hematopoietic Tet2-/- vs wild-type mice validation, disentangled causal proteomic perturbations from TET2 CHIP. Lastly, we identified plasma proteins shared between CHIP and CAD.

genetics↗

bioRxiv2021

A curcumin direct protein (DiPro) biosensor for cell-free prototyping

In synthetic biology, biosensors are routinely coupled to a gene expression cascade for detecting small molecules and physical signals. We posit that an alternative direct protein (DiPro) biosensor mechanism, could provide a new opportunity for rapid detection of specific chemicals. Herein, we reveal a fluorescent curcumin DiPro biosensor, based on the Escherichia coli double bond reductase (EcCurA) as a detection system. We characterise the EcCurA DiPro biosensor and propose enhanced curcumin fluorescence is generated through {pi}-{pi} stacking between protein and ligand. Using a cell-free synthetic biology approach, we use the EcCurA DiPro biosensor to fine tune 10 reaction parameters (cofactor, substrate, and enzyme levels) for cell-free biosynthesis, assisted through acoustic liquid handling robotics. Overall, we increase EcCurA-curcumin fluorescence by 80-fold. We speculate that a generic DiPro biosensor fluorescence mechanism can be further exploited for a wider range of chemicals that share intrinsic fluorescence and have a suitable binding protein.

synthetic biology↗