Biology subjects

Moreau, C. A.

Publications and source records attributed to Moreau, C. A..

3 recordsLinked to original sources

bioRxiv2023

Vaccination by single dose sporozoite injection of blood stage attenuated malaria parasites

An efficient malaria vaccine remains elusive. As an alternative to malaria subunit vaccines, vaccination approaches are currently explored using live Plasmodium parasites, either attenuated mosquito-derived sporozoites or attenuated blood stage parasites. Both approaches would profit from the availability of attenuated and avirulent parasites with a reduced blood stage multiplication rate. Ideally, such slow growing parasites would proceed normally through the mosquito but cause a self-limiting infection upon transmission. Here we screened gene-deletion mutants of the rodent parasite P. berghei and the human parasite P. falciparum for slow growth. In addition, we tested the P. berghei mutants for avirulence in mice and self-resolving blood stage infections, while preserving sporozoite formation and liver infection. Targeting fifty genes yielded seventeen P. berghei gene-deletion mutants with two mutants causing self-clearing infections in mice while retaining full transmissibility through mosquitoes. For those, infection of mice by a low number of blood stages, infected-mosquito bites or by single injection of sporozoites led to protection from disease after challenge with wild type sporozoites. Two of six generated P. falciparum gene-deletion mutants showed a slow growth rate. Slow growing, avirulent P. falciparum mutants will constitute valuable tools to inform on the induction of immune responses and aid in developing new as well as safeguarding existing attenuated parasite vaccines.

cell biology↗

bioRxiv2023

Using rare genetic mutations to revisit structural brain asymmetry

Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.

neuroscience↗

bioRxiv2022

Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence

Copy number variations (CNVs) are rare genomic deletions and duplications that can exert profound effects on brain and behavior. Previous reports of pleiotropy in CNVs imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, studies to date have primarily examined single CNV loci in small clinical cohorts. It remains unknown how distinct CNVs escalate the risk for the same developmental and psychiatric disorders. Here, we quantitatively dissect the impact on brain organization and behavioral differentiation across eight key CNVs. In 534 clinical CNV carriers from multiple sites, we explored CNV-specific brain morphology patterns. We extensively annotated these CNV-associated patterns with deep phenotyping assays through the UK Biobank resource. Although the eight CNVs cause disparate brain changes, they are tied to similar phenotypic profiles across [~]1000 lifestyle indicators. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

genetics↗