Mark Carrington

Molecular cell biology of trypanosomes.

The current diversity in eukaryotic life has evolved from the last common eukaryotic ancestor over more than one billion years. Early in this series of events, the group of protozoa that gave rise to trypanosomes diverged from the lineage that gave rise to plants, fungi and animals. So today, trypanosomes are the result of separate evolution of molecular processes over one billion years and they have accumulated many unique and inherently interesting aspects to their biology. The aim of the lab is to determine the molecular mechanisms that underlie some of the unique aspects of the biology of trypanosomes and other related protozoa.

Research objectives

• How does the trypanosome cell surface facilitate growth and survival in the mammalian host?

• How are mRNA levels altered in response to environmental queues?

• How has the structure of trypanosomatid genomes evolved to facilitate regulation of gene expression?

Key publications

Kelly S, Kramer S, Schwede A, Maini PK, Gull K, Carrington M (2012). Genome organization is a major component of gene expression control in response to stress and during the cell division cycle in trypanosomes. Open Biol., 2(4):120033. doi: 10.1098/rsob.120033

Lane-Serff H, MacGregor P, Peacock L, Macleod OJ, Kay C, Gibson W, Higgins MK, Carrington M (2016). Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor. eLife, 5:e13044. doi: 10.7554/eLife.13044

de Freitas Nascimento J, Kelly S, Sunter J, Carrington M (2018). Codon choice directs constitutive mRNA levels in trypanosomes. eLife, 7:e32467. doi: 10.7554/eLife.32467

MacGregor P, Gonzalez-Munoz AL, Jobe F, Taylor MC, Rust S, Sandercock AM, Macleod OJS, Van Bocxlaer K, Francisco AF, D'Hooge F, Tiberghien A, Barry CS, Howard P, Higgins MK, Vaughan TJ, Minter R, Carrington M (2019). A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis. PLoS Negl. Trop. Dis., 13(5):e0007373. doi: 10.1371/journal.pntd.0007373

Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK (2019). Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion. Nat. Microbiol., 4(12):2074-2081. doi: 10.1038/s41564-019-0589-0