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.
The Betancourt Lab hosted several students this summer, including two Nuffield students. These were Emily Clarke and Mecmillan “Mec” Rajaratnam, who used PCR to survey Wolbachia in flies.
Emily said about the placement: “I feel that I have benefitted greatly from my Nuffield placement and I have enjoyed every minute. I have gained a whole new platform of scientific skills, knowledge and techniques as well as been given an insight into the work that goes on within research science. Before beginning the placement, I did not really know what research science consisted of on a day to day basis however, experiencing this first hand has educated me on the works of scientific research daily. The project that I completed I thought was really interesting and I looked forward to attending every day of the placement to get some more results; in order to be one step closer to completing the project. Overall, I am so glad I was offered this fantastic opportunity and I definitely feel like I have gained so much from the experience.”
The Betancourt Lab also played host to second year undergraduate student Harry Collier, who carried out a project looking at the phenotypic effects of transposable element insertions in Drosophila. Harry also learned to code in Python during the course of his project.
Guest post by Rosie Maher, IIB PhD student
This summer I welcomed a 16 year old student from The King’s School Chester who took part in the Nuffield Research Placement Scheme. Before starting her placement Charlotte had plans to apply for medicine after finishing her A-levels but was curious about other medical related professions within biomedical science and biochemistry. Charlotte was appointed a position with myself, working in the Centre for Proteome Research within the Institute of Integrative Biology. Her four week project was titled “Identifying Proteins in Saliva to Diagnose Disease” and was a continuation of work that I have completed for my PhD.
During Charlotte’s four week stay she learnt three techniques that are used routinely in our lab; SDS-PAGE, zymography and western blotting. By the end of her placement she had produced some very interesting novel data, complementing the work that I have completed. It was a great experience to teach and supervise Charlotte, especially in an area of medical related science that she hadn’t heard of. I am now looking forward to her presenting this data at the Nuffield Celebration Evening in October.
This summer IIB’s Dr Dan Rigden hosted XJTLU student Xiaoyue Song:
Gut bacteria composition and activity can have big effects on human health and disease. There is therefore a lot of interest in understanding proteins and protein families encoded by the principal gut bacteria. Structural genomics has contributing by solving many structures but some of these have been deposited in databases without associated publications fully describing or predicting their functions. Xiaoyou has been focusing on a single family commonly found in gut bacteria, using a range of bioinformatics methods to try to predict its function. She strongly suspects that it is involved in carbohydrate metabolism and is currently trying to pin down the function further.
Guest post by Elysse Hendrick, undergraduate summer student
Working with supervisor Tom Price and his team, I carried out a research project investigating whether sleep patterns are affected by the battle of the sexes. The idea is that in species where females mate with multiple males, it is in the male’s interest if any female he mates with lays many eggs as quickly as possible, because after a while she will mate with another male who will father most subsequent eggs. So if males could force females to be active all day laying eggs, this would benefit the male. Normally, fruit flies are active only at dawn and dusk, so daylight egg laying might mean a female risks death due to predators or drying out. To test this, I put mated and unmated fruit flies into an activity monitor which, using an infrared beam, monitored the level of activity of each fly over a week. Entering this project, I had extremely limited experience of working with flies, so this project allowed the development of many new skills, including: sexing and identifying flies using microscopy, performing mating assays, food-making and maintaining fly stocks. Additionally, undertaking this project helped in gaining confidence, both in working in a different laboratory setting than usual with unfamiliar equipment (such as the activity monitor), and in working independently. Aside from my project, I also helped and worked alongside Tom Price’s team and attended team meetings, which helped me gain a valuable insight into the dynamic of a research group and the roles everyone plays. I enjoyed my project and working with the team very much and would definitely recommend taking part in a summer project.
Hinton Lab Interns with Professor Jay Hinton (left) and Dr Adam Roberts (right) after their project presentation
Annually, the Hinton Lab at the Institute of Integrative Biology invites A-level students to spend time learning new skills whilst working on a chosen project within our research lab. This year, the Hinton Lab Intern Week continued its collaboration with Dr Adam Roberts from the Liverpool School of Tropical Medicine and focused on the “Swab and Send” project, which aims to combat the very real threat that antimicrobial resistance poses to our health. The students looked for new antibiotic-producing bacteria by swabbing toys belonging to children of different age groups.
Over the course of the week of 23 July 2018, the four interns, supervised by PhD students Wai Yee Fong and Xiaojun Zhu, learned techniques that included making media for agar plates, inoculating bacteria, gram staining and microscopy. They also visited various parts of the Institute and the Liverpool School of Tropical Medicine. By the end of the week, the students had made some promising discoveries, and identified several new potential antibiotic-producing bacteria.
Hinton Lab Interns 2018. From left: Sam Cochrane; Catherine Lowe; Niamh Emond; Michael Campbell
Sharing their thoughts and reflections on the Intern Week, the students said the following:
- Michael Campbell: “I enjoyed the agar art session the most as it was fun and interesting to draw pictures using different types of bacteria. I also found the tours of the IIB genomics facilities and Centre for Cell Imaging very interesting.”
- Catherine Lowe: “It was interesting to see the different parts of the Institute and how they worked together, and how the lab works. I really enjoyed working in a research lab and doing something more than the theory which is all that we covered at school.”
- Niamh Emond: “What I liked about the Intern Week was getting the opportunity to do practical lab work that can potentially make a difference.”
Professor Hinton said: “It’s been a pleasure to welcome the next generation of scientists to work in our lab. It was inspiring to see the levels of interest of these students as they take on quite a challenging set of experiments. By teaming up with the ‘Swab and Send’ project, the students could discover bacteria that produce novel antibiotics. We are very grateful for the help of Adam Roberts, and for the financial support from the Wellcome Trust, which allows my lab to run this Intern Week”.
Guest post by Victoria Harman, Centre for Proteome Research at the Institute of Integrative Biology
On Tuesday 28th August, six members from the Centre for Proteome Research held a Victoria Gallery and Museum Summer Science Club session for local primary school children. The session, entitled ‘Marvellous Molecules’, began with a messy activity where the children were able to explore the components of ‘blood’. We used water beads, ping pong balls and square pieces of sponge to represent the red blood cells, white blood cells and platelets, respectively. The three components were bathed in water to represent blood plasma. All four components were correctly identified by the children and they even knew all the functions!
We then went on to explain that blood cells contain DNA sequences and that these sequences can be used to make proteins in our body. The children each selected a blood cell from the ‘blood’ mixture and opened them to reveal a laminated DNA sequence that coded for a different protein from different organisms. For example we had the DNA code for a protein in the venom of a cobra and the protein that causes oranges to ripen. Using this code the children could create DNA code bracelets where each nucleobase corresponded with a particular colour of bead. After creating the parent strand, using base coding pairs, the children were able to create the daughter strand. The children enjoyed this so much some made up to three bracelets!
Next we moved onto ‘DNA whispers’. This was a Chinese whispers activity using sentences about DNA to explain how it can sometimes be copied incorrectly causing errors. Some changes often don’t cause a problem, however, other errors (or mutations) can cause genetic diseases such as sickle cell anaemia. One of the sentences used in the game was “Even identical twins don’t have identical DNA” which got changed to “Even identical twins don’t have DNA”, proving a point about how small changes can have a big effect on the meaning of the sentence, or in terms of proteins, their function. We explained about sickle cell anaemia and the children were able to mix some blue water beads into the ‘blood’ mixture, representing the less oxygenated sickle cells. We explained that people with sickle cell anaemia can experience pain, but using some ‘marvellous molecules’ we can treat these symptoms. We looked at the structure of three of these molecules; paracetamol, ibuprofen and aspirin and got the children to make the structures out of paper and pipe cleaners.
We finished the session by asking the children questions about what they had learnt during the session. They were able to answer every question and were awarded with stickers for the correct answers.
We were all very impressed by the knowledge and enthusiasm of the children that attended the session and we look forward to helping out again next year!