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Sebastiaan van Heesch

27A. Functional characterization of microproteins in pediatric cancers

The human genome encodes thousands of evolutionarily young open reading frames (ORFs) translated from RNA that was presumed to be non-coding (e.g., van Heesch et al., Cell 2019; Mudge et al., Nature Biotechnology 2022). These recently emerged ORFs can code for small proteins termed microproteins.

Although the biological significance of these newly discovered putative microproteins is unknown, their young age and elevated expression during human development suggest a role in the recent evolutionary innovations that drive ‘human uniqueness’, such as the increased human brain size. However, when early development goes awry it can cause childhood cancer, a spectrum of rare but lethal diseases with an enormous impact on the lives of affected children and their families.

The goal of this project is to elucidate the relation between young microprotein expression, innovations in early human development, and childhood cancer. Can young microproteins play crucial roles in these processes, despite having only recently emerged from ancestrally non-coding DNA? The candidate will generate and analyze various types of sequencing data (Ribo-seq, RNA-seq) to discover childhood cancer open reading frames. The evolutionary origins of these genomic regions will be evaluated through bioinformatic approaches and putative microprotein roles in childhood cancer will be studied in the lab. The candidate will benefit from a worldwide network in Ribo-seq, gene annotation, and microprotein experts.

The van Heesch group combines wet- and dry-lab approaches and affinity with (or a background in) computational biology is highly recommended. Detailed understanding of gene expression regulation is required.

Necessary skill for this position:

  • Affinity with (or a background in) computational biology
  • Knowledge on gene expression regulation



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