MRC LMB’s Sofia Lövestam earns 2024 Harold M Weintraub Graduate Student Award for neurodegenerative disease work
A postdoctoral researcher at the MRC Laboratory of Molecular Biology has earned a prestigious award in recognition of PhD work that will aid the search for new treatments for neurodegenerative diseases.
Sofia Lövestam is one of the 2024 winners of the Harold M Weintraub Graduate Student Award, which recognises “outstanding achievement during graduate studies in the biological sciences.”
Sofia joined the LMB in Cambridge as a PhD studen in 2019, working with Sjors Scheres’ group in the Structural Studies Division and Michel Goedert’s group in the Neurobiology Division.
The groups’ studies have determined the structures of several amyloids from filamentous protein aggregates. The the accumulation of these characterise a number of neurodegenerative diseases.
Typically, researchers have relied on post-mortem brains to study amyloid filaments, which has limited progress.
Sofia sought to tackle this with her PhD by developing amyloid assembly reactions in vitro to replicate the same structures observed in diseases brains.
Scientist thought progressive accumulation of amyloids resulted from prion-like spreading, with existing filaments providing seeds that template the growth of further filaments.
But when Sofia first mapped the structures of the in vitro seeded assembly of recombination alpha-synuclein filaments with seeds from brains with multiple system atrophy (MSA), she was surprised to discover they yielded new structures. Her discovery was recognised with the 2022 FEBS Open Bio Article Prize.
She then turned her attention to tau filaments, using spontaneous in vitro assembly of recombinant tau to make the same structures as those seen in brains with different tauopathies.
A broad range of methods and conditions were required to make tau filaments, along with extensive analysis using electron cryo-microscopy (cryo-EM).
But Sofia successfully identified truncated tau constructs and in vitro assembly conditions that created identical tau filaments to those found in Alzheimer’s disease and chronic traumatic encephalopathy (CTE).
The achievement has huge potential to broaden the access to more researchers studying these diseases, and Sofia has shipped her tau constructs to laboratories all over the world, while also providing guidance to help several other research groups replicate her results.
Sofia then turned her attention to analyse the molecular mechanisms of amyloid formation in Alzheimer’s and CTE in a time-dependent manner. She learned, contrary to the prevailing opinion, that tau assembles through many intermediate structures and she discovered a shared first intermediate amyloid (FIA) present in the pathway towards Alzheimer’s and CTE filaments.
This study is the first tangible structural characterisation of intermediates of amyloid filament formation and reveals a complexity to the process not previously recognised.
Sofia used cryo-EM to solve more than 300 structures of amyloid filaments during her PhD and expanded our understanding of the molecular mechanisms driving amyloid formation.
By discovering a number of new avenues for research, the LMB says her work “could prove crucial in the design of new drugs to target different neurodegenerative diseases”.
Sofia, who won the 2022 Perutz Student Prize, was awarded the Harold M Weintraub Graduate Student Award by the Fred Hutchinson Cancer Center based in Seattle, USA.
The award is named after Harold (Hal) M Weintraub, who made major contributions to the understanding of how gene expression leads to cell differentiation; work that helped found the modern field of epigenetics.
Hal was an LMB alumnus, working in its Cell Biology Division as a scientific visitor in the early 1970s before heading to Princeton University and then the Basic Sciences Division at Fred Hutch in 1978. He worked there until his death in 1995 at the age of 49.
