PIPages
Labs

Crystal Conn

University of Pennsylvania, PA·Biochemistry

A gene's instructions have to be read twice: first copied from DNA into RNA, then translated by ribosomes into protein. It turns out the amount of RNA in a cell often fails to predict how much protein gets made, which means RNA-based tests of tumor samples miss part of the picture.

Fields

Biochemistry

Genetics

Biology

Topics

RNA translation

translation initiation

non-canonical initiation

Grants
1 known grant, through Jul 2029

What they work on

  1. Map the post-transcriptional layer of gene expression missing from annotated genomes by cataloging alternative ribosome initiation sites, combining unbiased ribosome sequencing with proteomic profiling to define the full oncogenic proteome including unannotated micropeptides.
  2. Identify the RNA-binding proteins and RNA sequence domains that select specific messenger RNAs for increased translation during disease progression, independent of any change in their transcript levels.
  3. Test how chemical modifications of RNA and the positioning of RNA within the cell influence which transcripts are chosen for non-canonical translation initiation.
  4. Characterize how growth and adaptive signaling cascades rewire translation during shifts between cell states modeled in cancer progression, linking signaling inputs to changes in ribosome start-site usage.

More about the research

Large surveys have also turned up thousands of small proteins and protein variants that were never annotated in reference genomes. This work asks how cells control which RNAs get translated, where along an RNA the ribosome starts reading, and how that control lets cells rapidly rewire themselves as disease progresses.

Why it matters

Because RNA levels alone poorly predict protein output, tumor profiling based on RNA has limited power to guide therapy. Mapping which RNAs are translated, where ribosomes start, and which modifications control that choice could reveal proteins and micropeptides unique to malignant cells, offering candidate targets for diagnostics and RNA-based therapeutics that differ by disease type.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Dynamics of RNA regulation and noncanonical translation between cell states

NIH · Aug 2024 – Jul 2029

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Christopher Fraser

University of California-Davis, CA·Biochemistry

Determine which intermediate steps of translation initiation act as kinetic checkpoints controlling messenger RNA recruitment, using ensemble fluorescence assays that follow recruitment in real time in a reconstituted human system of purified ribosomes and initiation factors.

Jean-Denis Beaudoin

University of Connecticut, CT·Genetics

Generate detailed maps of the epitranscriptome, the chemical modifications on RNA, across the native zebrafish transcriptome during the maternal-to-zygotic transition, and test how specific modifications affect gene expression.

The school

University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.

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