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Trevor Forsyth: Transthyretin amyloidosis - from molecules to patients

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From: 2020-11-10 15:30 to 16:30
Place: The Belfrage lecture hall at BMC D15 OR online/zoom
Contact: kajsa_m [dot] paulsson [at] med [dot] lu [dot] se
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Transthyretin amyloidosis - from molecules to patients

FÖREDRAG

A lecture with Professor Trevor Forsyth. Professor Forsyth’s research mainly is focused on the study of biological systems, notably amyloid formation, but his involvement in infrastructure, analysis, and method development has alsoresulted in research into soft matter and structural chemistry.

Abstract

Human transthyretin (TTR) is implicated in several fatal forms of amyloidosis. Many mutations of TTR have been identified; most of these are pathogenic, but some offer protective effects. The molecular basis underlying the vastly different fibrillation behaviours of these TTR mutants is poorly understood. Using a combination of neutron and X-ray diffraction, native mass spectrometry and modelling studies, we have proposed a mechanism whereby TTR can form amyloid fibrils via a parallel equilibrium of partially unfolded species that proceeds in favour of the amyloidogenic forms of TTR. It is suggested that unfolding events within the TTR monomer originate at the C-D loop of the protein, and that destabilising mutations in this region enhance the rate of TTR fibrillation. Furthermore, it is proposed that the binding of small molecule drugs to TTR stabilises non-amyloidogenic states of TTR in a manner similar to that occurring for the protective mutants of the protein. These results are being followed up for other clinically relevant mutants of TTR.  In collaboration with the Amyloidosis Centre at the Royal Free Hospital in London, this research is being pursued in the context of proteolysis effects that are believed to be involved in destabilising TTR, and in studying ligand interactions that may offer better protection to patients. Parallel studies are also being planned in which the behaviour of recombinant mutants of TTR are compared with the TTR isolated from the plasma of patients afflicted with the same mutation(s).

Registration

Due to the Covid-19 situation there is a limit of maximum 30 participants on-site and the seats will be reserved to the participants that are first to register.

For those who want to attend on-line we will have a Zoom-channel open during the seminar.  

Register to attend onsite
Register to attend via zoom/online

Tid: 

2020-11-10 15:30 till 16:30

Plats: 

The Belfrage lecture hall at BMC D15 OR online/zoom

Kontakt: 

kajsa_m.paulsson@med.lu.se