Seems like a good day for a "Remember your scientific heroes" thread. Today I'm thinking about Richard Lerner, because I'm reading this bonkers new Cell paper. Like any self-respecting Cell paper, this one is chock full of the latest/greatest tech, even Fig 1 is nuts www.cell.com/cell/fulltex... - ThreadSky

jsrosenblum.bsky.social • 1 day ago

Seems like a good day for a "Remember your scientific heroes" thread.

Today I'm thinking about Richard Lerner, because I'm reading this bonkers new Cell paper.

Like any self-respecting Cell paper, this one is chock full of the latest/greatest tech, even Fig 1 is nuts

https://www.cell.com/cell/fulltext/S0092-8674(24)01344-8?dgcid=raven_jbs_etoc_email

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jsrosenblum.bsky.social•1 day ago

The paper tells the modest story of figuring out in which organelle every single human protein lives. The authors seemlessly tag thousands of proteins with a handle that allows them to gently isolate entire organelles, then use the wonders of mass spectrometry to see what other proteins came along.

jsrosenblum.bsky.social•1 day ago

But of course, they have the capacity to do this analysis under whatever conditions they want, so they flex their scientific muscles & infect the cells with a virus and see what happens. tl;dr a boatload of stuff happens.

But what does this paper have to do with Richard Lerner?

jsrosenblum.bsky.social•1 day ago

Well a key method used in the new paper, the versatile tag that could be used to isolate all those complexes arose from Richard's work. Richard was an MD who was keenly interested in how structure begat function. After Bruce Merrifield (another hero) developed solid phase peptide synthesis ...

jsrosenblum.bsky.social•1 day ago

Richard (and others) started to use peptides to figure out how antibodies worked. Before ~early 1980s, it was absolute dogma that most peptides had no discrete structure. Richard (& wife Nicky) published an amazing paper in 1982 showing just how wrong this idea was.
https://pubmed.ncbi.nlm.nih.gov/6176330/

jsrosenblum.bsky.social•1 day ago

They selected influenza virus hemagglutinin (HA), a protein whose sequence & xtal structure had been determined 2 & 1 year(s), respectively, prior. HA is cleaved to form HA1 (pink and yellow in fig) and HA2 (blue), which then disulfide bond & form a 2-chain monomer.

Pink peptides all elicited ...

jsrosenblum.bsky.social•1 day ago

antibodies (Abs) that could bind to native HA. Not only did this result lead to the generation of monoclonal antibodies against HA that have been used in 1000s of papers for a massive variety of different techniques using HA-tagged proteins, it led to other Abs to study 100s of other proteins & ...

drsimoncook.bsky.social•1 day ago

Nice thread!

jsrosenblum.bsky.social•1 day ago

Thanks!

vvsmider.bsky.social•23 hours ago

Thank you for this post. Richard brought me to Scripps. He was an out of the box thinker. And great person- when my (now late) wife got an aggressive cancer he pulled me into his office and told me not to worry about grants or papers -“do what you need to do, we’ve got your back”…

jsrosenblum.bsky.social•22 hours ago

Ha - out of the box doesn't quite capture it!

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