Christopher Steel exploring the role of proteoglycans and glycosaminoglycans in aortic aneurysm and dissection funded by Biochemical Society supervised by Hannah Davies and Jill Madine
Aortic aneurysm is a bulge in a section of the aorta. This causes weakening of the aortic wall and increased risk of the blood vessel bursting. A number of biochemical factors can complicate the local environment of an aorta which then has a direct consequence on the mechanical function of the vessel. One factor reported to affect the integrity of the vessel wall is the concentration and distribution of proteoglycans (PGs) and glysaminglycans (GAGs), particularly ‘pooling of PGs’ which may compromise the aorta wall and lead to delamination, aortic aneurysm, and dissection.
In his project Chris investigated the levels of PGs and GAGs in human tissue obtained during aortic surgery at Liverpool Heart and Chest Hospital using a range of gel-based techniques and dot-blots and employed immuno-staining to investigate the distribution of GAGs within the medial layer of the aorta wall. Data is being correlated with existing data on biomechanical properties and biochemical composition of collagen and elastin, along with clinical characteristics for the same patients to assess whether PG and GAG distribution could be contributing to altered aortic wall integrity in disease. PGs and GAGs could provide a future therapeutic biomarker to predict risk of aortic disease and rupture.
Ravina Mistry, summer student working with James Torpey, supervised by Jill Madine and funded by Biochemical Society
Investigating peptide inhibition of alpha-synuclein as a potential therapeutic option for Lewy Body diseases
The two most common forms of dementia after Alzheimer’s disease are Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). These diseases are associated with intracellular inclusions of misfolded protein aggregates called Lewy bodies (LBs). The major protein component of LBs is the misfolded protein α-synuclein (asyn). Asyn and its associated aggregation/misfolding pathway is therefore a therapeutic target for these diseases. Collaborators in Bristol have identified a ten residue peptide that can prevent asyn aggregation and in turn prevent its associated toxicity. James had carried out NMR experiments to investigate the interaction between peptide and asyn and gain insight into the mode of action of the peptide in preventing aggregation. This data suggested that over time the peptide undergoes a structural rearrangement that is only detectable by a highly sensitive technique such as NMR, and that this is required before the peptide and protein are able to interact. This has implications for understanding the role of asyn aggregation in disease-associated toxicity and how it can be targeted therapeutically.
In her project Ravina investigated whether the peptide can also interact with and prevent aggregation of the six known disease associated mutants of asyn. Furthermore, she also used modified versions of the peptide (using amino acid substitutions) to further probe the mode of action and enhance the future progress of this peptide into a viable therapeutic avenue. She gained experience in a range of techniques including protein expression and purification, NMR, isothermal titration calorimetry, electron microscopy and fluorescence assays.
On Thursday 29th of June, Marie Phelan of the Technology Directorate (NMR Metabolomics) and member of the Biochemical Society helped out the Society at the Lancashire Science Festival held in the Halls of University of Central Lancaster, Preston. The event was attended by primary and secondary schools from Cheshire, Merseyside, Greater Manchester and Lancashire with the aim to engage and inspire the next generation in science technology engineering and mathematics (STEM). The Biochemical Society ran several activities in order to inform and debate genome editing including recent advances such as CRISPR-Cas9 technology with pupils as young as 6 engaging in DNA editing methodology and ethics.
Figures: Some of the Biochemical Society volunteers speaking to local pupils at the Lancashire Science festival. Pupils learn about “Scientific Scissors”. Science Festival Exhibitors Main Hall
Guest post by Hannah Davies
The Neuroblastology project run with UTC Life Sciences School and funded by the Biochemical society has finished! Billions of cells grown, 25+ students participated, tens of compounds tested, 9.5/10 scored – overall, we all had a (neuro)blast!!
Here is Dr John Dyer, teacher at LLS-UTC:
This has been an incredibly successful project that has proved to be very popular with students from across the year groups. The students have gained valuable skills in cell culture and aseptic technique as well as a range of transferrable skills such as leadership, time management (in order to care for the cells), experimental design and evaluating and improving upon techniques and procedures. The level of enthusiasm and engagement that students have shown has been incredible and many students have happily given up time at lunchtime breaks and after school in order to tend to the cells or collect data. This enthusiasm and engagement has certainly been increased by the fact that Hannah spent time training the students at the start as well as coming in on a number of occasions to provide technical expertise and support with experimental design. Students regularly commented that they have enjoyed these sessions and found it useful to have direct contact with active researchers. Perhaps the most striking thing for me was how disappointed the students were when some of their cells got infected. However, they responded brilliantly by developing their procedures in order to minimise the risk of further contamination. This sort of resilience, coupled with the level of care, accuracy and precision required during this project will prove invaluable to students at the start of their scientific careers.
Although the project has come to and end for this year, we are delighted to report that it will continue next year as part of UTC’s enrichment curriculum! We are also in the process of moving aspects of the project online so more schools will be able to interact and participate so watch this space!!
If you would like to read more about the project, please see the following link for the Biochemical Society final report…
By Luciane V. Mello
One way we can contribute to young people’s enthusiasm for science is by working with their teachers, e.g. through continuing professional development schemes like STEM Insight.
Last February in partnership with the Biochemical Society we received Maria Saeed, from Blackburn College, for her Insight into University experience placement.
The week was a great experience and I am now putting into practice what I have learnt. For example, I am working on developing a numeracy skills pack for all learners, and I am hoping to do several practical sessions in the same format I saw at the university that worked very well… I believe the scheme has been invaluable in developing my own teaching practice and the links between the college and Liverpool University in the long-term.
I’m delighted to report that Maria Saeed was nominated for the ENTHUSE Further Education Award, an event organised by STEM Learning and the Wellcome Trust to recognise the impact that teachers and technicians have on their pupils, colleagues, schools, colleges and peers. I would like to thank all members of staff who helped me to offer Maria a wonderful experience during her week in the Department of Biochemistry (IIB) and in the School of Life Sciences: Amal Abdulkadir, Fabia Allen, Peter Alston, Andy Bates, Rob Beynon, Elaine Connor, Caroline Dart, Claire Eyers, Pat Eyers, Karen Fitzsimons, Blair Grubb, Phil Harrison, Keith Hatton, Joscelyn Sarsby, Jerry Turnbull, Susanne Voelkel and Mark Wilkinson.
A successful team work! We are now prepared for other teacher visits so if you are interested, get in touch.
Dr. Guadalupe Gómez Baena, a postdoctoral research associate in the Centre for Proteome Research in the Institute of Integrative Biology has won a Scientific Outreach Grant from the Biochemical Society to support the costs of running a Science Club titled ‘Learning to think like scientists’ at New Park Primary School. The club will run during the academic year 2016-2017 and is aimed at promoting the understanding of the scientific environment in primary school children.
Engaging children in science at an early stage is important, not only to assure a solid foundation for the future scientific generation, but also to develop significant skills and attitudes important in learning and understanding. The club will demonstrate why science is important and what is it like to work as a scientist, while teaching basic aspects of science and research.
The Centre for Proteome Research is actively involved in a number of activities aimed at disseminating the importance of science. This activity will be delivered by members of Centre for Proteome Research who are registered as STEM ambassadors.
Guest post by Hannah Davies
A bit about the project…
We are living longer – which is great – however this also increases the incidence of diseases associated with aging. One such condition is Alzheimer’s disease. It is estimated that the cost of dementia to the UK economy is expected to be £59.4 billion by 2050. As such there is a drive to improve diagnosis and generate therapeutic agents that will tackle this devastating disease.
This project (supported by a Biochemical society outreach grant) will raise awareness of the societal implications of an ageing population and dementia alongside demonstration and explanation of some of the types of research that is currently ongoing to increase our understanding of the processes of ageing. A key area of research into understanding the ageing brain is development of in vitro model systems to provide an environment to test new diagnostic and therapeutic agents prior to clinical trials. The emphasis of this project is to give students an understanding of the important role that these cell systems can play in understanding the ageing brain.
This project will have two stages. The first stage will involve collaboration with John Dyer at Liverpool life sciences UTC to develop methodology and teaching materials around cell culture models in the context of the ageing brain. The second stage of the project will be to deliver the workshops/plenaries/practical sessions on the ageing brain to other local schools in the area.
Liverpool life sciences UTC is a specialist school for life sciences and has many students aspiring to work in health and science disciplines. Students are assigned to a selected ‘pathways’ that enables them to tailor their school activities to their future aspirations. One aspect of this is the innovation factory where students can design and test research questions. Currently, they are still developing their labs to accommodate the experiments dreamt up by the students using old instrumentation donated from industry and academia. At present, they have equipment suitable for cell culture (CO2 incubators and laminar flow hoods) but they do not have the expertise or reagents to enable experiments with live cells despite interest from many of their students.
Where we are up to…
Cell culture demo at the UTC
Checking on cells
On Monday 18th January 2016 after several months of discussions and preparation we took proliferating SHSY-5Y (a neuronal cell-line) cells into UTC. Armed with protocols, risk assessments and lab coats we taught some keen and able representatives from years 11, 12 and 13 how to care for the cells in our absence. The students will culture the cells until they have sufficient for their ambitious experiments. With so many students from several years interested they will need to passage the cells several times to get the volume/number required. Just before February half term they will harvest the cells and perform their experiments. The students were excellent and I have every faith they will do a great job! Wish them luck!!
Look out for updates (#Neuroblastology) to see how they get on and what exciting experiments they have planned…