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Adams, I.

Publications and source records attributed to Adams, I..

3 recordsLinked to original sources

Deep Receptor Scanning Reveals General Sequence Constraints on GPCR Biosynthesis

G protein-coupled receptors (GPCRs) mediate a variety of signaling pathways and are the most common pharmacological targets. While advances in structural biochemistry have provided deep functional insights into key receptors, many of the 800+ human GPCRs remain understudied. We introduce a versatile "deep receptor scanning" platform that can be used to experimentally characterize 766 human GPCRs and 174 known GPCR splice variants in parallel. We use this platform to quantitatively characterize the relative abundance of canonical and alternative receptor transcripts, their translational efficiency, and the plasma membrane expression of each receptor in the context of a recombinant pool of HEK293T cells expressing individual GPCRs. We then employ machine learning to identify specific structural features that modulate GPCR expression. This experimental platform and informatic approach are compatible with a variety of assays and can be used to efficiently explore the biochemical and pharmacological properties of the GPCRome.

biochemistry↗

A retroviral origin of vertebrate myelin

Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains and greater morphological diversity. Here we report that RNA level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show RNLTR12-int-encoded non-coding RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int like sequences (which we name RetroMyelin) are found in all jawed-vertebrates and we further demonstrate their function in regulating myelination in two different vertebrate phyla (zebrafish and frogs). Our study therefore suggests that retroviral endogenization was a key step in the emergence of vertebrate myelin.

neuroscience↗

Characterising maize viruses associated with maize lethal necrosis symptoms in sub Saharan Africa

Maize lethal necrosis disease (MLN) is an emerging disease in East Africa caused by the introduction of Maize chlorotic mottle virus (MCMV). Recent activity seeking to limit spread of the disease is reliant on effective diagnostics. Traditional diagnostics applied on samples with typical field symptoms of MLN have often given negative results using ELISA or PCR for MCMV and Sugarcane mosaic virus (SCMV). Samples collected in the field with typical MLN symptoms were examined using next generation sequencing (NGS). SCMV was found to be more prevalent than suggested by targeted diagnostics. Additionally, the panel of samples were found to be infected with a range of other viruses, seven of which are described here for the first time. Although not previously identified in the region, Maize yellow mosaic virus (MYMV) was the most prevalent virus after MCMV. The development of targeted diagnostics for emerging viruses is complicated when the extent of field variation is unknown, something that can be negated by using NGS methods. As a result we explored MinION technology which may be more readily deployable in resource poor settings. The results show that this sequencer can diagnose known viruses and future iterations have the potential to identify novel viruses.

microbiology↗