I wasn’t even able to download the applications I’m supposed to review - I get an error message from the system.

Cells are subject to mechanical forces that shape their function and survival through a process termed “mechanotransduction.” While well studied outside of the brain, neuronal mechanotransduction is understudied despite exposure of the brain to vascular flow, injury, and disease.

2/9

This study was an outgrowth of our original finding that tau destabilizes the nucleoskeleton in neurons and drives nuclear envelope blebbing and invagination:
www.cell.com/current-biol...

3/9

Claira subsequently discovered that nuclear tension is reduced in a cellular model of tauopathy:
www.frontiersin.org/journals/agi...

4/9

Led by proteomics, we now hone in on a specific protein, emerin, that is elevated in cell culture models of tauopathy. Emerin is a central regulator of nuclear mechanotransduction that allows cells to sense and respond to cellular force.

5/9

Claira finds that emerin overexpression in cultured neurons is sufficient to drive toxicity, increase filamentous actin, and induce nuclear invagination, cellular phenotypes that also occur in settings of tauopathy.

6/9

She further finds that emerin relocalizes from the nucleus to the cytosol in a cellular model of tauopathy, where it has increased interaction with cytoskeletal regulators.

7/9

Our findings lay the groundwork for future studies on the role of emerin and altered nuclear mechanotransduction in neurodegenerative tauopathies and highlight an emerging function of emerin as a regulator of nuclear mechanotransduction in neurons.

8/9

It’s never too early. Just write the grant and see what you think. That’s when all the good ideas come anyway.

Interested in transcriptome complexity, RNA mods, polyA tail length, or retrotransposons? Are you a data junky who likes to mine new resources? Our Nanopore-based direct RNA sequencing study in Drosophila (in the context of health and #tau pathogenicity) is for you.
2/5

De novo transcriptome assembly reveals previously missed complexity, including abundant transcripts with retained introns. Transcripts with long polyA tails are enriched for signal transduction and MAPK signaling, while those with short polyA tails are enriched for translation/ATP metabolism.
3/5

We find that m6A modification is highly variable across transcripts, with enrichment at the 5'UTR and transcription start sites. Highly m6A-modified transcripts are associated with immune system processes, while those with lower m6A are associated with homeostatic translation.
4/5

We leverage long reads to map source loci for active retrotransposons, with copia elements showing particularly high m6A, then compare all these findings (m6A, polyA, retrotransposons, etc.) to a fly model of tauopathy. Check out the paper to see what intrigues you.
5/5

While we are particularly interested in candidates who focus on cellular and molecular mechanisms driving neurodegeneration and/or specialize in human brain analyses, we encourage applicants from any research area that aligns with the mission of the center.

We promote discovery and innovation in neurodegenerative disorders by supporting a diverse community of experimentalists, theorists, engineers, and clinicians.

Our focus is to bridge the gap between scientific discovery and clinical application by uniting pioneering researchers with dedicated clinicians to accelerate the translation of discoveries into new diagnostic approaches and therapies.