Biology subjects

Griffin, D. K.

Publications and source records attributed to Griffin, D. K..

4 recordsLinked to original sources

bioRxiv2021

Human Pre-Implantation Embryos Are Permissive to SARS-CoV-2 Entry

The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. We note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. Using fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, we observe robust infection of trophectoderm cells, and this permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.

developmental biology↗

bioRxiv2020

A universal formula for avian egg shape

The birds oomorphology has far escaped mathematical formulation universally applicable. All bird egg shapes can be laid in four basic geometric figures: sphere, ellipsoid, ovoid, and pyriform (conical/pear-shaped). The first three have a clear mathematical definition, each derived from expression of the previous, but a formula for the pyriform profile has yet to be inferred. To rectify this, we introduced an additional function into the ovoid formula. The subsequent mathematical model fits a completely novel geometric shape that can be characterized as the last stage in the evolution of the sphere--ellipsoid--Hugelschaffers ovoid transformation applicable to any avian egg shape geometry. Required measurements are the egg length, maximum breadth, and diameter at the terminus from the pointed end. This mathematical description is invariably a significant step in understanding not only the egg shape itself, but how and why it evolved, thus making widespread biological and technological applications theoretically possible.

evolutionary biology↗

bioRxiv2020

Individual human genomes frequently contain variants that have epistatic interactions

Coevolution has been widely studied between species and has an important role in our understanding of biological function. For proteins there has recently been interest in the identification of positions within proteins that have coevolved including their use for modelling protein structure. Such studies focus on the identification of coevolving positions (or evolutionary couplings) within multiple sequence alignments of proteins from many species. Here, we exploit large human genome resources to investigate if it is possible to use genetic variation data from a single species, human, to identify positions within proteins that have coevolved. We combine the 1000 genome project genetic variation data with protein structural data to identify variant-variant interactions within individual human genomes. We find >4,000 combinations of variants that are located close in 3D protein structure and >1,200 in protein-protein interfaces. Many variant combinations include compensatory amino acid changes (e.g. maintaining charge/functional groups), thus supporting that these are coevolutionary events. Our study highlights that it is possible to identify coevolution within a single species. Given the important role that genetic variation plays in causing disease it is important for variant interpretation and precision medicine to consider the gestalt effects of variants rather than individual variants in isolation.

genetics↗

bioRxiv2019

An improved pig reference genome sequence to enable pig genetics and genomics research

The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete and unresolved redundancies, short range order and orientation errors and associated misassembled genes limited its utility. We present two annotated highly contiguous chromosome-level genome assemblies created with more recent long read technologies and a whole genome shotgun strategy, one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. These highly contiguous assemblies plus annotation of a further 11 short read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.

genomics↗