See our lab website here: tierpsy.com
We explore the molecular mechanisms underlying nervous system function by finding genes and gene networks that affect behaviour.
The goal of behavioural genomics is to understand the mapping between genome variation and behaviour. However, technology for sequencing and perturbing genomes is advancing more rapidly than our ability to assess all of the consequences of genetic perturbation. To help redress the imbalance between measures of genotype and phenotype, we are developing high-throughput imaging platforms to capture complex behavioural sequences and automated algorithms to interpret them.
Motor behaviour is a useful phenotype because it is the principal output of the nervous system and has previously been used to find genes with roles in synaptic transmission, neural development, and many kinds of sensation among other things. The nematode worm C. elegans is a great model for behavioural genomics in part because of its relatively simple and exceptionally well-characterised nervous system. Its locomotion is sufficiently complex to reliably identify subtle differences between mutants yet simple enough to quantify nearly completely. Well-developed reagents for imaging gene expression and neural activity make for a tight loop between hypothesis generating screens and hypothesis testing functional experiments.
et al., 2023, Systematic creation and phenotyping of Mendelian disease models in C. elegans: towards large-scale drug repurposing, Elife, ISSN:2050-084X
et al., 2023, Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals., Genet Med, Vol:25, Pages:90-102
et al., 2022, Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications, American Journal of Human Genetics, Vol:109, ISSN:0002-9297, Pages:1421-1435
et al., 2022, Megapixel camera arrays enable high-resolution animal tracking in multiwell plates, Communications Biology, Vol:5, ISSN:2399-3642
Nambyiah P, Brown AEX, 2021, Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment, Scientific Reports, Vol:11, ISSN:2045-2322, Pages:1-10