By Heather Hobbs
BRINGING YOU THE LATEST NEWS & EVENTS FROM THE SCIENCE INDUSTRY Building a Genetic Map for Parkinson’s
A team from the Francis Crick Institute, UCL and Cambridge University has been awarded $7.7million to identify the genetic and biological factors that cause Parkinson’s disease.
The team, co-led by Sonia Gandhi, Group Leader of the Crick’s Neurodegeneration Biology laboratory, has received the grant from ASAP (Aligning Science Across Parkinson’s). This global research initiative funds teams that are working on understanding the basic mechanisms that contribute to the development and progression of Parkinson’s disease.
By using advanced imaging methods to look for single molecules, or oligomers, in the brain as indicators of early onset of the disease, the researchers aim to build a map of the cells fi rst affected and the conditions progression. By looking at all the genes expressed in those specifi c cells, they will build a model that shows how genetic factors affect pathways that cause Parkinson’s. The aim is to then modify these genes in human stem cells, to better document and understand their effects over time.
There’s a huge gap of knowledge about the earliest stages of neurodegenerative diseases like Parkinson’s but if we
can identify which cells start to lose function fi rst, we could pinpoint the underlying cause,” said Sonia Gandhi.
“We’ve brought together a team of physical chemists, geneticists, data scientists and neurobiologists, who all have their own expertise and bring different techniques to the table. Through this powerful combination, we hope to be able to provide more detail about the underlying genetic causes of Parkinson’s and why some brain cells are susceptible to the disease while others remain resistant.
“Critical to the ASAP initiative is building a unique resource, a Parkinson’s brain map and also making it freely available to others, which we hope will help the research community to develop new theories about the disease, explore its mechanisms and identify new therapeutic targets.”
Professor Nicholas Wood from UCL Queen Square Institute of Neurology, said: “We are delighted with this major investment in basic Parkinson’s research. We will use state of the art molecular microscopic tools to identify the cells that are principally affected by the disease and use detailed transcriptomic analyses to understand the molecular events that lead to neurodegeneration.”
Sonia Gandhi
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Study Shows Compound Signifi cantly Prevents Progression of Diet-Induced Non-Alcoholic Fatty Liver Disease
Rom et al report that the oral administration of the simple tri-peptide, DT-109 (Patent US8664177B2), prevents both development of non-alcoholic fatty liver disease (NAFLD) and late stage fi brosis in a murine model of diet-induced non- alcoholic steatohepatitis (NASH). The study titled, ‘Glycine- based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome’ was published in Science Translational Medicine on 2 December 2020.
DT-109 is a 3 amino acid, orally active peptide, that stimulates release of intestinal GLP-1. Dr Eugene Chen and his team at the University of Michigan identifi ed DT-109 as having dual glucose/ lipid-lowering effects and potently lowering steatohepatitis and fi brosis in a long-term pre-clinical NASH model. Applying advanced multi-omics approaches, the team identifi ed underlying mechanisms by which DT-109 protects against
NAFLD. These included modulation of the gut microbiome, stimulation of lipid utilisation in the liver and the production of one of the most protective antioxidants, glutathione.
Dr Oren Rom, the study lead author stated: “We thought outside the box and focused on understudied aspects linking dysregulated amino acid metabolism to NAFLD. Our studies not only provided metabolic explanations for impaired glycine metabolism in NAFLD, but also identifi ed a novel glycine- based treatment.”
“This promising study shows that certain glycine-based treatments attenuate experimental NAFLD by stimulating hepatic fatty acid oxidation and glutathione synthesis and therefore warrants clinical evaluation beyond initial animal model and in-vitro data. Further studies would be well justifi ed in clinical trials to continue to deliver on the positive outcomes thus far,” said Mathew Diggle FRCPath,
PhD DLSH&TM MSc - Consultant Microbiologist, Associate Professor and member of the International Working Group for Diabetic Foot Infection.
DT-109 has been licensed from the University of Michigan by Diapin Therapeutics LLC. Dr Bruce Markhan, CEO of Diapin stated: “DT-109 has been designated as a lead NASH compound and is currently being evaluated in preclinical IND enabling studies and developed in chemical manufacturing control. We see this as a breakthrough molecule for the treatment of NASH and other co-morbidities associated with metabolic syndrome.”
More information online:
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Dundee Scientists Scoop EU funding Award understanding cellular responses to environmental stress.
“We are studying almost unexplored areas of cell biology which has immense potential for ground-breaking discoveries. StressHUb will explore the functions of branched heterotypic ubiquitin chains (HUbs) in cellular stress responses. These branched HUbs play important roles in the physiology of human cells, however, their functions have not been defi ned because of the complex nature of these modifi cations and the lack of ways to study them,” said Dr Kulathu, MRC Investigator and Group Leader at the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC PPU).
“We will develop novel tools and methodologies which will reveal the cellular machinery that makes these modifi cations, how they are formed in response to stress, and their roles in resolving cellular stress. This knowledge can then be used to develop drugs to treat various diseases where cellular stress is not resolved, such as neurodegeneration, chronic infl ammatory diseases and cancer.”
Dr Yogesh Kulathu
University of Dundee researchers Dr Yogesh Kulathu and Dr Jorunn Bos, leading investigations into plant cell biology and in provision of plant protection respectively, have been awarded over €4 million by The European Research Council (ERC) as winners of an ERC Consolidator Grant.
Dr Kulathu’s €2.1 million project, StressHUb, will investigate fundamental principles regulating stress at the cellular level and develop new technologies and methodologies for
Dr Bos, a principal investigator in the Division of Plant Sciences and the James Hutton Institute based in Invergowrie, will use the grant worth almost €2 million for developing new ways to provide crop protection against insects. “This project is building on years of work by members of my team, past and present and without them this would not have been possible. “
The key questions that drive APHIDTRAP are building on previous fi ndings that aphids can actively promote host susceptibility using effector proteins.
Dr Jorunn Bos
The function of these effector proteins is based on association with host proteins and modifi cation of their activity.
“The next step is to try and understand how these protein- protein interactions take place, and what the downstream consequences are with regards to susceptibility.” said Dr Bos.
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