Molecular Neuroscience Group
Shining Light on Neurodegeneration
Our preprint shows α-synuclein lipid-associated fibrils are more readily taken up into neurons and lead to different vesicle and fibril morphology compared to synthetic lipid vesicles.
7 October 2022
In our latest paper in Journal of the American Chemical Society we show Aβ42 aggregation increases the temperature of live cells due to exothermic fibril elongation and demonstrate its potential as a diagnostic screening assay for small molecule inhibitors. We further demonstrate using molecular dynamics simulations, that heat retention by Aβ is favoured under intracellular-mimicking conditions. Find an article discussion the publication here.
Find our paper here.
13 June 2022
In our latest paper in Analytical Chemistry we use two-photon fluorescence lifetime microscopy (2P-FLIM) and phasor plot analysis for label-free identification of different amyloid protein fibrils and their polymorphs by their unique fluorescence lifetimes.
Find our paper here.
13 June 2022
Our latest paper in Stem Cell Res Ther we show the use of biofunctionalised bacterial cellulose as an in vitro scaffold to promote the growth of stem cell-derived cell types. Hopefully this work will be useful in the treatment of Parkison's disease and other neurodegenerative conditions.
Find our paper here.
16 November 2021
Our latest paper in PNAS combined experimental data with molecular dynamics to show that short hydrogen bonds enhance nonaromatic protein-related fluorescence.
Upon heating, L-glutamine converts to a new structure, L-pyro-amm. L-pyro-amm has a similar structure to L-pyroglutamine, but differs due to the presence of short hydrogen bonds, an associated ammonium ion (released upon conversion), and charge reorganization. These components lead to increased fluorescence in the new structure. Insite into these mechanisms of intrinsic fluorescence offer the possibility of designing novel biomaterial for applications in optical sensing or the design of novel biocompatible catalysts.
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Find our paper here.
19 May 2021
Our researchers Sagnik, Ana and Miranda show super resolution imaging and calcium imaging, along side electrophysiology and spike classification from spontaneous neuron activity using transparent MEAs.
A transparent microelectrode array (MEA) technology based on the conducting polymer PEDOT:PSS enables state-of-the-art optical imaging along with electrophysiology. The electrodes maintain low noise under laser illumination and allow the detection of single unit activities from multiple putative neurons.
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Find our paper here.
12 May 2021
Our preprint 'The mobility of water influences protein misfolding' shows ions influence water motions which are inextricably linked to protein dynamics and therefore misfolding propensity.
Can the presence of different ions and water mobility in cells influence disease outcome?
2 Feb 2021
Chyi's review on intracellular thermometry probes and their application to study thermodynamic properties of cells and energy flow in protein aggregation is published in ChemBioChem and featured as the technology of the month in Trends in Biochemical Sciences.
We highlight different nanoscale thermoprobes that have enabled intracellular temperature gradients to be visualised. Intracellular thermometry is proposed as a tool to quantify energetics involved in amyloid-beta 42 aggregation, a hallmark of Alzheimers' disease.
6 Jan 2021
A new mechanism on how endoplasmic reticulum reshapes is revealed by a combinatorial method of super-resolution imaging, optogenetic tools and machine-learning from LAG-MNG:
The endoplasmic reticulum (ER) is dynamically regulated by lysosomes by VAPA dependent membrane contacts.
In neuronal axons, lysosomes drive ER tubules to move along axons thus connect ER fragments to be a continuous membrane structure.
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Find our paper here.
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17 Dec 2020
Our new publication 'Purification of Recombinant α-synuclein: A Comparison of Commonly Used Protocols'shows our choice of purification method for a-syn influences the outcome of downstream assays
We therefore wonder whether the choice of purification method e.g. 'harsh' treatments such as boiling, can influence the dynamic ensemble of the monomeric protein, changing the conformational distribution, and influence downstream assays, such as cell response or aggregation rate.
29 Nov 2020
A new paper on Αβ purification led by Amberley Stephens is out now.
We provide a method for the purification of recombinant label-free amyloid-β using commercially available reagents and without the need for a freeze drying step which induces oligomerisation.
1 Oct 2020
Many congratulations to our group leader, Gabi, on her promotion to Reader!
27 June 2020
We are very excited to share our latest research published in Nature Communications on alpha-synuclein conformational dynamics!
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We investigated the monomeric conformation of aSyn in different conditions and found that the more exposed the N-terminus of the protein becomes, the more aggregation-prone it becomes.
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Sequence alterations such as the presence of post-translational modifications and familial point mutations that lead to early-onset Parkinson's disease also lead to differing exposure of the N-terminus, linked to aggregation propensity.
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This paper is led by Amberley Stephens and Maria Zacharopoulou and is a result of a big collaboration cohort. Many congratulations to all!
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04 June 2020
Our new article sheds light on the coupling between mitochondrial impairment and α-synuclein pathology!
We show that protein homeostasis in mitochondria plays a major role in α-synuclein aggregation, as a disruption of intramitochondrial proteases leads to aggravated α-synuclein seeding.
The paper is led by ​Janin Lautenshläger, and includes work performed by many LAG and MNG members. Many congratulations to all!
8 May 2020
If you're interested in nuclear architecture or stem cell differentiation, check the new preprint on bioRxiv led by Colin Hockings and Chetan Poudel!
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The article introduces a new method based on fluorescence lifetime to measure chromatin compaction in any cell, live or fixed, without genetic modification. It is a result of the collaboration between members of the Laser Analytics Group and the Molecular Neuroscience Group. Many congratulations to all who contributed!
3 May 2020
Ioanna Mela's article on DNA-origami as an antimicrobial delivery agent is published in Angewandte Chemie.
The paper is led by the Laser Analytics Group's postdoc Ioanna Mela and includes collaborations with MNG.
Many congratulations to authors: Ioanna Mela, Pedro Vallejo-Ramirez, Stanislaw Makarchuk and Clemens Kaminski!
15 April 2020
Despite the national quarantine we continue our work remotely - more new exciting projects on the way!
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March 2020
Review paper on fluorescent protein imaging is now published in the Physical Biology journal!
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Well done, Meng, Gabi and Clemens!
11 February 2020
Congratulations to Gabi and Amberley for their article being selected for PCCP 2019 hot articles list!
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You can find this paper here
01 February 2020
Dr Amberley Stephens's article is on bioRxiv now! ​
The study reveals possible mechanisms behind intrinsic fluorescence in glutamine-like structures.
The paper can be found here
23 January 2020
Miranda Robbins has passed her viva!!
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Congratulations to Dr Miranda Robbins for passing her PhD viva!
16 December 2019
Philippa Hooper has passed her viva!!
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Congratulations to Dr Philippa Hooper who passed her viva in only 2 hours!
13 September 2019
Our review paper ”The Cellular Environment Affects Monomeric α-Synuclein Structure” is May's featured paper in Trends in Biochemical Sciences!
Read the paper and find more information here.
May 2019
Dr Gabi Kaminski Schierle was interviewed by the Naked Scientists about how the "build up of Calcium could lead to Parkinson's".
Read more here.
27 February 2018
Researchers in the Molecular Neuroscience Group have found that excess levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson’s disease.
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Read more here.
19 February 2019
