Ammonium Signalling in Dimorphic Fungi

Ph. D. ThesisAmmonium is a preferred source of nitrogen utilised by fungi. In some fungi ammonium availability is sensed by ammonium transporters belonging to the Amt/Mep/Rh superfamily. During ammonium limiting conditions these transporters trigger a signalling cascade to induce a morphological change. The molecular basis for signalling and the extent to which these transporters are conserved are important questions within the field. We have investigated morphological change in response to ammonium availability in two divergent fungi. The wheat pathogen Zymoseptoria tritici and the human pathogen Cryptococcus neoformans serotype D JEC20 (MATa) and JEC21 (MATa). We show that low ammonium dependent filamentation is ZtMep2 independent and that mutants lacking ZtMep3 acquire a severe growth defect during ammonium sufficient conditions. Moreover, Ztmep3D mutants display a different type of filamentation which may be as a result of ammonium starvation as opposed to ammonium signalling. ZtMep3 does however act as an ammonium sensor when expressed in yeast, to regulate pseudohyphal growth, despite lacking the conserved twin-histidine motif previously believed to be essential for signalling. Furthermore, the dual loss of ZtMep2 and ZtMep3 renders Z. tritici hypervirulent in the wheat infection assay suggesting that a lack of internal ammonium is the trigger for virulence. In C. neoformans, we show that hyphal growth, induced during ammonium limiting conditions, is CnAmt2 dependent and that the expression of the CnAmt2N241A mutant in yeast uncouples transport from signalling. Therefore, signalling by CnAmt2 is not the consequence of internal ammonium metabolism and is due to the physical act of transport. Fundamental questions now exist as to why these two diverse fungi have adopted different modes of ammonium signalling and about how prevalent these starvation responses are throughout fungi.BBSRC DTP, NUBI, formally ICAM

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p