Dario R. Alessi
Discovered PDK1, the master kinase that switches on Akt/PKB and the AGC-kinase family downstream of PI3K signalling
BSc, University of Birmingham (1988) · PhD, University of Birmingham (1991) · postdoc, University of Dundee (Philip Cohen lab, 1991–1997) · Professor of Signal Transduction, University of Dundee (since 2003) · Director, MRC Protein Phosphorylation and Ubiquitylation Unit (since 2012)
Principal investigator page, MRC Protein Phosphorylation Unit, University of Dundee ↗
In 1997, working in Philip Cohen's Dundee lab, Alessi purified and characterised PDK1 — the kinase that phosphorylates Akt/PKB on its activation-loop threonine (Thr308) in response to PI3K-generated lipids, switching the enzyme on. PDK1 turned out to be a hub: it also activates p70 S6 kinase and other AGC-family kinases, placing it structurally upstream of, and mechanistically intertwined with, mTOR signalling. He later extended this into the mTORC2 side of the pathway: with Jose M. Garcia-Martinez, his group showed that mTORC2 phosphorylates not only Akt's hydrophobic motif but also that of SGK1 (2008), meaning mTORC2 sits at the top of two parallel growth-factor-response kinases, not one. The following year the same collaboration produced Ku-0063794, one of the first genuinely selective ATP-competitive mTOR inhibitors — blocking both mTORC1 and mTORC2 — which became widely used to dissect which of mTOR's effects depend on each complex.
Alessi trained in biochemistry at the University of Birmingham, then moved to Dundee for postdoctoral work with Philip Cohen — a lab already central to phosphorylation research — where he stayed on as an independent program leader from 1997. He became Professor of Signal Transduction at Dundee in 2003 and was appointed Director of what is now the MRC Protein Phosphorylation and Ubiquitylation Unit in 2012.
His current work centres on LRRK2 and the phosphorylation pathways implicated in inherited Parkinson's disease, alongside the Division of Signal Transduction Therapy, a long-running collaboration between the Dundee unit and major pharmaceutical companies. He is a Fellow of the Royal Society (2008) and the Academy of Medical Sciences, and was appointed OBE in 2023.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2008 | M | mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1) GAR2008 Shows that mTORC2 controls the hydrophobic-motif phosphorylation and activation of SGK1, extending mTORC2's reach beyond Akt to a second growth-factor-responsive kinase. |
| 2009 | M | Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR) GAR2009 Characterises Ku-0063794 as a specific ATP-competitive mTOR inhibitor that blocks both mTORC1 and mTORC2, becoming a standard tool for separating the two complexes' effects. |