Grants awarded to Modupeh Betts and Aku Kalizang'oma
Congratulations to MPRU PhD students Modupeh Betts and Akuzike Kalizang'oma for their successful grant applications to the UCL Doctoral Students' Small Grants Scheme!
Modupeh applied with Seth Jarvis (UCL Genetics Institute) and Aku applied with Mislav Acman (UCL Genetics Institute). Read abstracts of their research proposals below:
A Hybrid Approach to Generating a High-quality Complete Genome Sequence of Clinical Streptococcus pneumoniae Serotype 6B
Modupeh Betts and Seth Jarvis
Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia, meningitis, and sepsis worldwide. Pneumococcal disease and transmission is preceded by successful colonisation of the human nasopharynx. The nasopharyngeal niche is characterised by harsh biochemical conditions and competition for nutrients with other mucosal commensals. To assess bacterial response to this environment both in-vitro and ultimately in-vivo, we plan to use RNA-Seq to describe the transcriptome of the pneumococcal serotype 6B. The 6B strain is commonly carried, causes disease, and has been used in the controlled human infection model by our collaborators. This will enable us to understand how pneumococcus adapts its gene expression to specific conditions of the nasopharyngeal environment and may identify potential vaccine targets to prevent colonisation, and ultimately transmission and disease. However, a well annotated and contiguous reference genome assembly is essential for efficient transcriptomics analysis. Such a genome sequence is lacking for strain 6B. Here, we propose to use a hybrid approach to sequence and re-annotate a complete and unambiguous high-quality genome of 6B. We will use a combination of long-read-low-coverage (PacBio®) and short-read-high-coverage (Illumina®) sequencing technologies to exploit the strengths of both platforms in resolving bacterial genomes. Publication of a high-quality genome assembly of a clinical strain of S. pneumoniae will be valuable to the wider scientific community, advancing our knowledge of pneumococcus.
The application of novel computational methods to identify Streptococcus interspecies exchange of antimicrobial resistance determinants in Africa
Akuzike Kalizang'oma and Mislav Acman
Malawi is a low-income African country greatly affected by pneumococcal diseases such as pneumonia, meningitis and sepsis. Treatment of bacterial infections is becoming more challenging due to an increase in antimicrobial resistance (AMR) strains. One example is the growing resistance of S. pneumoniae which has been aided by the interspecies exchange of AMR genes with the commensal S. mitis. Despite its importance, very few S. mitis genomes have been sequenced. In this collaborative project we will generate sequencing data from S. mitis isolates and explore the extent and mechanisms of exchange of AMR genes with S. pneumoniae. Isolates of the two bacterial species originate from the same nasopharyngeal swabs from previous Malawian pneumococcal carriage studies. However, in these studies only S. pneumoniae genomes have been sequenced. This project will use whole genome sequencing (WGS) to characterise S. mitis populations. Furthermore, novel computational biology methods developed by the Balloux group at UCL Genetics Institute (UGI) will be used to study the exchange of AMR genes. The interfaculty collaboration between UGI and the Division of Infection and Immunity will address UCL’s Grand Challenge of Global Health (antimicrobial resistance).