Writeups
Meeting Write-Ups (Descending Order)
19th SWFM // 27th March 2024
The 19th South West Fly meeting was held on 27/3/24 at the University of Bristol. The first talk, by SWFM new member, Dr Stefan Harmansa who has a Wellcome CDA at University of Exeter and who is studying basement membrane mechanics shape growing tissues. He is interested in how different shapes of organisms arise, with D’Arcy W Thompson a hundred years ago proposing that principles and forces influence development of shape and morphology. Stefan has been using the Drosophila wing disc growth is study these processes studying the concepts of morpho-elasticity and planar an-isotropy growth. He used Drosophila mutants to pick apart mechanisms underlying each. Next up, Fardina Rahimi from Prof Herman Wijnen lab at the University of Southampton discussed the control of oviposition in the soft fruit pest Drosophila suzukii by Drosophila-associated bacteria. She highlighted that the spotted wing fruitfly had invaded North American and Europe since 2008, targeting ripening soft and stones fruit via adapting to cold climates and being a benefitting migrant of climate change. She found Suzukii don’t produce so many offspring when melanogaster are there. She also investigated the effect of odour trapping with attractive odours and antibiotic assays to treat Suzukii’s gut biome, showing lactobacteria deter them from laying on plates. Next new SWFM, Dr Alice French discussed her planned work at University of Bristol poising the question What can Drosophila teach us about sleep? She gave examples of Mallard ducks, sleeping in groups with ducks on the outside of the group sleeping with inside half of brain asleep and eye shut. While also highlighting that people are more likely to wake up when their name is mentioned. She helped develop the Ethoscope tracking system with measures fly activity/immobility as a metric of sleep. The machine allows one to sleep deprive flies and test arousal (sleep depth), by tracking if the fly sleeps and then turning the tube to wake it up. She is using different promoter lines and optogenetics to probe the neural circuits underlying sleep and arousal signals. Finding that some odours are more likely to awake the fly than others, namely the ones it eats or one it has been trained with. She finds that dopamine and the memory circuit are involved in processing salient signals in sleep. After tea, Dr Nick Priest talked about Jingbo Lui thesis work at University of Bath on Genetic correlations and the evolution of innate immunity. They are interested in: if we can feed flies supplemental nutrients to offset climate change, How innate immunity evolves and what the physical constraints limiting evolution? Their assays involve counting the number of eggs different females lay over their 40-80 day lifespan and then plotting the data against each other. He measured the effect of ageing on fecundity and lifespan and then looked to see why effect Gram + and – bacteria and viruses had on both variables. He found a gene called Dif is required in this process by induction of a subset of antimicrobial peptide genes. Lastly, Dr Edgar Buhl from Prof James Hodge lab from University of Bristol spoke about his work Decoding the fly’s circadian membrane clock. He has very carefully electrophysiologically recorded from clock neurons at different times of day in flies compared to mice. He has found rhythms in different electrophysiological parameters in both animals and is using computational modelling to understand their role in circadian rhythms. Importantly the comparative neuroanatomy of fly versus mouse neurons is important for differences in propagation of the circadian signals, namely the action potential through the different clock neurons. Edgar is trying to work out the ion channels underlying the changes in these membrane signals and how they relate to the molecular clock. Discussion of all things fly continued over refreshments kindly provided by the Genetics Society.
18th SWFM // 9th January 2024
The 18th South West Fly meeting was held on 9th January 2024 at the University of Bristol.
Dr Mark Hanson (Wellcome ECA / SNSF research fellow, University of Exeter – Penryn) “When the microbiome shapes the host: the Achilles Principle of immune evolution.” Project started in Prof Bruno Lemaitre lab Lausanne), works on anti-microbial compounds, secreted by many organisms to protect them from environment (eye tears). Haemolymph micro molar range of anti-microbials, fundal, gram + and – bacteria cause changes in 2 NF-Kappa-B pathways. AMP response CRISPR out all the AMP genes in flies. Systemic injections of bacteria, ECC15-GFP bacteria, wildtype get rid of green, mutants in AMP do not. Genetic Reference Panel, Polymorphism in Diptericin A AMP was key AMP. Effect of AMPs on microbiome (flies mostly Acetobacter and Lacobactera) , Diptericin B specific against Acetobacter. Fruit fly eaters DptA and B and Mushrooms just A and plant neither. Diversity of food sources is allowed by diversity of AMPs.
Prof Helen White-Cooper (Cardiff University) "Making two types of sperm – a tale of two moths."
Moths make 2 types of sperm, Emma Moth was a Masters students who worked on the Moths, sent by James Wakefield and Piece. Germline stem cell makes spermatogonia>amplifying mitotic divisions> 1o > 2o spermatocytes > haploid spermatids > elongated spermatids into mature spermatozoa.
Takes 9 days (drosophila)
Eggs>Larvae (Eusperm normal sperm with nucleus) > Pupae (Parasperm, no nucleus), > Adult (parasperm). Pupae and Adult still have eusperm. Sperms have different proteomes.
Some CRISPR-Cas9 RNAI in Lepidopteran models (Bombyx mori). Galleria mellonella parasite of bee hives, and immunology. Looked at Sex-lethal RNA-binding protein needed for sperm development.
Lin-9 transcriptional regulator required for meiotic progression.
Cyst RNA-seq analysis, to look for differentially expressed genes in larvae v pupae in Galleria. David enrichment analysis 300 upregulated in normal sperm.
CCdC63 paralog between 2 different sperms
Sex lethal and Taf4 differentially expressed
Lepidoptera pest control is important
Independently evolved in pseudoobscura and lepidoptera
Some crabs
Covergent evolution in response to selective pressure eg.g. sperm competition
Rachel Sellick (Dr Michael Taylor, Professor Anne Rosser and Dr Mariah Lelos Cardiff University) “Hunting(tin) for genetic interactions: Development and Degeneration in Huntington's Disease” Mef2 and Huntingtin: development and degeneration in HD.
Autosomal dominant. 2.17:10000 lethal in 20 years.
Lact of HTT mouse model is lethal. Mislocalisation of HTT in human brain. Alterations in junctions.
GMR and elav>Gal4 expression of HTT
7 Rhabodmers in control and only 3-4 Rhabdomers in HTT
20-50 CAG repeats WT, 93 mild and Q120 repeat strong HTT transgene.
Mef2C is embryonic lethal, reduced hippocampal and cortical function (dysfunction if HD). Changes neuronal survival. KO mouse memory deficit and anxiety behaviour.
Mef2C-RNAi suppresses HTT Q93 overexpression. Mef2C overexpression enhances HTT effect. With elav-Gal4 they die. Inducible promoter.
The earlier mutant HTT is expressed the more vulnerable the neurons.
Developmental in origin.
So no HTT gene in flies, In HD do you get changes in Mef2C (GWAS)
Dr Ben Housden (University of Exeter) “Drug repurposing using Drosophila cell culture models of disease’
Forward genetic screen for all genes that suppress disease phenotype. Translate.
But model hits only work in fly context and don’t translate to humans. Genetic background heterogenous but molecularly conserved. Non-duplicated genome. Neurofibromatosis type 1, NF1, autosomal dominant tumour syndrome, 1:3500 and NF1 gene mutations. Tumours on nerves causes blindless. Plexiform, lethal cancers. One drug, that is NF1 ras blocks. But Toxic. CRISPR in a NF1 mutation, made null mutants. NF1 null, mutant all genes, whole genome wide RNAi screen, looks for genes that when knocked down makes NF1 null S2 cells live longer. Variable dose analysis. Then do network analysis. Autophagic flux, GFP-reporter, to look at autophagocytic. Synthetic lethal interaction. Half of autophagy
Relative viability across a dose response curve of drugs. Pharmacology controls. KD target remove drug effect? Or opposite OX enhance suppression.
Chloroquine increases autophagy, nSyb-Gal4, dcr
Autophagy Drug conc dropped in human.
Concs vary between fly, mouse and human. Genome wide screens not possible now, company folded.
VDA. Therefore use a pooled library project. Get library with effect, then split in 10 and look for 1/10 that has effect and keep on going.
Plot a line y axis = NF1 viability and x = wildtype ones that have longest distance from NF1. CG8080 positive hit.
ALS motorneuron disease, 1:100,000, onset >60 year. 3-5 year life expectancy from diagnosis. No effective treatments. TDP43 or TDP43-M337V overexpression
Bonus gene rescues ALS TREM gene
Kidney cancer CDK4/6 inhibitor Phase 1b
TSc mizoribine
NF1
S2 cells from 1970s, human cell lines from NF1 tumour v WT cell lines. Scwann
Prof Herman Wijnen (University of Southampton) 'Sleep position in Drosophila and its circadian control' Jonathan Anns, Adam Claridge-Chang lab in Singapore (Michael Youngs lab postdocs microarrays. Different conscious state readily reversible, reduced responsiveness and change in typical posture. Daily rhythmicity. Homeostatic regulation. Various proposed functions: synaptic homeostasis, energy balance and waste clearance. Poor sleep is associated with poor health outcomes.
Human EEG, EMG EOG
Flies, 5 minutes of inactivity. Danger of confound of other sleep inactive state.
Cyc01 removes circadian component of sleep. Increased arousal threshold during rest. Reversible. Sleep deprivation leads to a sleep rebound. Species specific position. Rest posture and place preference in insects. Hendricks Segal J Bio Rhythms 2000, pose is different closer to food. And also in DAM tube 96% time in food half of tube. Donelson et al 2012 towards food. Both males and females.
Beam breaking high throughput and video tracking medium throughput.
Walking ball. Low throughput, high resolution and imaging
Identify fly posture in sleep
Truman show and Drosophila. Trumelan 48hr long high resolution videos. Like Claridge chang learning apparatus in Miesenboek lab. 10fps, learning algorithm. Using tracking software like deep lab cuts and match to qualitative judgement of sleep by human, then use best model. Males have siesta females do not. Compare to DAM assay, by drawing imaginary line in middle and compare to tracking software. Also look at angle of fly body position. Not very informative.
Does make a different if and what food is at the end. Like to face away from food.
LL phase, lose rhythm.
Actin suction pad, to hang on leaf.
Circadian stationary ceiling occupancy is abolished in LL.
Map clock genes and neurons in process.
Circadian rhythms NF-KBeta controls immunity. Feeding in bedbugs.
17th SWFM // 28th June 2023
The 17th South West Fly meeting was held on a very hot and humid afternoon on 28th June 2023 at the University of Bristol. The first talk was by Dr Jake Turley who is working in Dr Helen Weavers and Prof Paul Martin’s labs at University of Bristol who spoke about deep learning analysis of cell behaviour during wound healing. He is using mathematics and machine learning to understand cell migration during wound healing. Using eCadherin-GFP and histone-RFP embryo movies after making wound, the videos are analysed with imageJ plugins and AI Watershed algorithm with deep learning model. This allowed accurate identification of cell boundaries and measuring of cell velocity. They are studying the signalling pathways: DUOX, calcium and JNK signalling in haemocytes moving to injuries.
Next Amaia Alcalde Anton from Dr Stephen Montgomery and Professor James Hodge labs, University of Bristol spoke about her functional analysis of candidate genes linked to mushroom body evolution. She studies Heliconius butterflies that show a form of pollen feeding and spatial navigation behaviour called trap lining. Their unique dietary adaption allows them to have a longer lifespan (6-8 months) and an expanded mushroom body for enhanced memory, attention and olfaction. Amaia is looking to see if this is due to increased neuroblast and MB neuron numbers. She is screening candidate genes identified bioinformatically as being differentially expressed in Heliconius and testing their role in flies using olfactory shock memory and automated MB neuron counting.
Next Dr Owen Peters from Cardiff University spoke about his lab’s work on glial function of phosphoinositide metabolising enzymes in fly models of Alzheimer’s disease and injury. A lot of new genes associated with Alzheimer’s are expressed in microglia like TREM2 and APOE4. Flies do not have microglia (immune cells) but do have wrapping glia as well as ensheathing and cell body/cortex glia. His student studied a rare coding variant in PLCG2 522 Proline to Arginine which is AD protective, using a CRIMIC fluorescent reporters line in PLCG2 which expressed the variant and also UAS-aos:AB42 using Repo-Gal4 to look at genetic interactions. They found the fly ortholog, of PLCG2 called small wing when knockdowned delays engulfment of severed axons of OR85e olfactory neurons.
After tea, Dr Alice French from CRICK, Imperial and now Bristol University spoke about the divergent evolution of sleep functions. Why do we Sleep? And why do bats sleep 19 hrs and elephants only 2-3 hrs. Previous work from her lab showed male and female isogenic flies vary greatly in total sleep. Alice has looked at Drosophila sub species using the ethoscope to measure response to sleep deprivation and circadian regulation of sleep in Drosophillids, which are usually active at dawn and dusk (crepuscular) with a 24hr period. Surprisingly Drosophila virilis cannot maintain circadian rhythm in constant darkness. Looking at sleep deprivation (mechanical), only Drosophila melanogaster, shows rebound, homeostatic and compensatory sleep. The sleep stages were identified via hidden Markov models. Interestingly when male – male sleep deprivation was used melanogaster, yakuba, simulans, sechellia etc then showed rebound with increases in synaptic protein brp in the rebounding sleep specific species. Likewise synaptic and memory genes go up with deprivation and knockdown of these genes decreased sleep deprivation. Alice is now looking at whether dopamine synthesis is involved in rebound.
Lastly Dr Fisun Hamaratoglu from Cardiff University spoke about a non-neuronal role for Tau in epithelial homeostasis. She looks at wing disks, which have an apical and posterior side with engrailed splitting the wing disc into compartments. Homeostasis maintains the disc compartments. Apterous which is Greek for without wing, is expressed in dorsal wing pouch cells which are Apterous positive and wingless is expressed at the D-V boundary. When they express ectopic Apterous they get protrusions into the wrong compartment and showed that actomyosin accumulates and rounds up and eliminates clones. They are also looking at the role of EphA2 in cell migration and specification as a model of cancer. Lastly Tau is highly expressed in brain but not in wing disc. When you knock out Tau you get changes in dLMO expressing lines of the wing disc via Tubulin.
16th SWFM // 16 May 2023
The 16th South West Fly meeting was held at Bristol University on Wednesday afternoon 10th May 2023. Dr Pedro Joaquim Faria Jacob from lab of Prof Scott Waddell, FRS, University of Oxford) discussed how Opponency within the dopaminergic system codes probability. Flies need to take account of internal states and the sensory world which can be assessed using the aversive memory paradigm. If you perform massed training you can present an odour, say 3 times paired with 1x, 2x or 3x pairing with shocks. The flies can keep track of the number of times they received the shock and how great the stock was. It is known the fly mushroom body mediates memory and within these neurons those that form the gamma lobes are important. Based on optogenetic experiments, the team suggest the gamma5 and Beta’ 2A may compute probability. Next, Dr Daniel Maddison from Dr Gaynor Smith’s lab at Cardiff University talked about how COPI controls mitochondria-ER contact site formation in neurons. They performed a EMS screen to access mitochondrial quality control live in flies expressing mito-GFP in sensory neurons of the wing. They identified alpha-Cop unit mutations, that caused a decrease in mitochondria, and caused neurodegeneration after 7 days of expression of the mutation. The mutation caused increase calcium, smaller cristae in mitochondria and ac change in mitochondria-ER contact in fly and mammalian SY cell line. After tea, Dr Meg Stevens from Dr Ben Housden’s lab at Exeter University talked about a synthetic lethal screen that identified existing autophagy drugs with selective viability effects on Neurofibromatosis type-1 (NF1) model systems. The team studied dNF1-KO flies and NF1 deficient cells and found that the anti-malarial, chloroquine was able to slow NF1 tumours. Lastly, Dr Saurabh Chaudhary from Prof. Helen White-Cooper Lab at Cardiff University talked about Testes-specific gene regulation in Drosophila. There are many male specific genes including 300 uniquely expressed genes in the brain and 1300 uniquely expressed genes in testes. The team wanted to know what makes the primary spermatocytes stage so transcriptionally active. They used the Testes Meiotic Arrest Complex (TMAC) to identify binding motifs and perform next generation sequencing. They used Yeast 2 hybrid screens to test potential interactions and are using CRISPR to make mutants and enhancer traps for candidate genes.
After the talks we discussed all things fly outside in the sun, with refreshments generously provided by the Genetics Society.
15th SWFM // 11 January 2023
The 15th South West Fly meeting was held at Bristol University on Wednesday afternoon 11th January. Dr Jan Kropf from Prof Gero Miesenböck lab at University of Oxford discussed his novel research on a Spectral Chronometer for Interval Timing in Drosophila. He is investigating how the mushroom body (MB) circuit encodes time during learning by electrophysiologically recording MB response to odours across time. This involves having a fly on a ball on a microscope rig and presenting it with 3 odours, sequentially, giving a shock punishment with one time point, the fly associates this time point with punishment and tries to run away from the shock paired odour. A MB circuit involving an APL giant neuron feedback loop was proposed. Next, Dr Zeynep Okray also from Oxford and Prof Scott Waddell lab discussed how multisensory learning expands memory engrams. Not only can flies associate reward or punishment with odours but they can also do so with colours. Furthermore, in the wild and here for the first time in the lab, they are demonstrated to be able associate different combinations of odours and colours. Zeynep and Dr Pedro Joaquim Faria Jacob propose a MB, dopamine and DPM/serotonin circuit elucidated using optogenetic activation, inactivation and GCaMP recording experiments.
So, we now know flies are brainer than we thought, but down the other end they also have interesting sperm, newly PhD’d, Dr Fiona Messer from Prof Helen White-Cooper at Cardiff University discussed spermatogenesis in Drosophila pseudoobscura involving the development of three sperm morphs. Fiona discussed how sperm showed heteromorphism with two types of sperm in the same fly, fascinatingly this evolved twice in flies, but also in fish, mollusks other insects. She looked at the pseudoobscura’s different sperm size, structure, nuclei number and transcriptional profiles of its spermatocyte cysts.
After tea, Fiona Defty from Dr Shamik dasGupta’s lab at Bristol University gave a interesting talk entitled a Brave New Virtual World for Drosophila. So, rats, ants, bees and flies return to nest or food source and to do so use path integration or body orientation involving distance calculation and place memory. Fiona has created a virtual fly arena that tracks a fly’s movements and can allow presentation of sensory stimuli. This allows odours to be given when the fly meets objects in the virtual arena. She is using this to look at place memory and the neural circuits that mediate it. From PhD student to a talk given by head of School, Prof James Wakefield from Exeter University on using the Drosophila syncytial blastoderm embryo to understand the molecular basis of branched microtubule nucleation. He has pioneered the use of in vivo movies to study mitosis by fluorescently labelling Tubulin-GFP, Histone-RFP, EB1-GFP, etc. His team then live imaged mitosis, with a cleavable affinity purification protocol to isolate intact protein complexes required for chromosome segregation. They then identified all the components, which are confirmed and quantified with Westerns. This has led him to identify mitosis-specific phosphorylation sites in augmin which he is now characterising further. The meeting ended with more fly and social discussions generously supported by the Genetics Society.
14th SWFM // 29 June 2022
The first talk was on the neural circuit for spatial navigation in Drosophila by Dr Ilaria D’ Atri from Dr Shamik DasGupta’s lab at the University of Bristol. Illaria showed flies can do landmark and path integration. e.g. desert ants can forage then find shortest path back. Flies use optic flow, odometer (i.e. speed meter), celestial compass, polarised light and path integration to achieve this. The group have made a novel ring-shaped maze which allows the steps of the fly to be measured as well as a delivery of a reinforcement. Using this memory paradigm, Ilaria is dissected the central complex circuitry that mediates the behaviour which will then be characterised with GCaMP imaging. Next, Amy Preston a talented Master’s student in Dr James Hodge’s lab at the University of Bristol, discussed the in vivo characterization of candidate genes associated with Alzheimer’s disease using Drosophila. This research team have been screening GWAS and EWAS Alzheimer hits in flies. Using bioinformatics, fly genetics and behavioural assays they are screening candidate genes for Alzheimer disease relevant phenotypes such as rough eye degeneration, climbing, circadian rhythms, sleep and memory. She is comparing the effect of neuronal v glia misexpression and has a range of new mutant phenotypes and mechanisms. Staying with the theme of behaviour but switching to another insect, Connor Tyler from Dr Herman Wijnen’s lab at the University of Southampton) discussed the circadian behaviour and pest-plant interactions of the diamondback moth. The Diamond back moth causes $5 billion damage to brassica annually. With climate change is it is seasonally expanding its cosmopolitan range. Connor is characterising their circadian behaviour using well-developed Drosophila clock assays and is determining the interaction between the moth’s body clock, immune system, mating and feeding behaviour. By doing so they hope that they maybe able to understand or find away to disrupt the moth’s ability to mate or find and lay on the crops its offspring devours.
After tea, Hannah Clarke from Dr Gaynor Smith’s lab at Cardiff University discussed her PhD work investigating the distinct neuronal and glial roles of the AD risk gene Wwox in Drosophila. There are 900000 cases of Alzheimer in UK with 1 person diagnosed every 3 minutes. Recently the WWOX gene has been associated with AD. Hannah has been knocking down or overexpression Wwox in neurons and glia and looking at lifespan, climbing, circadian rhythms, sleep and memory. To probe the synaptic mechanisms that may underlie the behavioural changes seen she has performed Electro-Retino-grams. As well as Single cell RNA-Seq of different fly AD model. She is now performing an enhancer/suppressor screen between Wwox and RNA-seq genes and co-expressed human AD causing genes. The last talk by Michaela Joyce from Dr Giorgio Gilestro’s lab at Imperial College asked Do all drosophilids count sheep? She addressed this question using a cross-species investigation of Drosophila sleep. Using the ethoscope activity tracking system she monitored the sleep of Drosophila melanogaster (wild caught and Canton-S) v virilis (bigger) v simulans v sechelia v yakuba. Measuring their response to sleep loss, caffeine, male-male fighting and homeostatic mechanisms. She saw a number of differences which might involve synaptic proteins, tyramine and were considered in the context of the different environmental niches the sister species had evolved. As always people asked lots of questions, informally discussed future directions, shared reagents, potential positions and made new contacts and friends over pizza and drinks kindly provided by the Genetics Society.
13th SWFM // 9 March 2022
The 13th South-West Fly meeting was held at Bristol University on 9th March, 2022
Dr Giuliana Clemente from Dr Helen Weaver’s lab at University of Bristol described how a PI3K-Calcium-NOX axis primes leukocyte Nrf2 to limit systemic aging and sustain host viability. Giuliana presented beautiful molecular genetics and imaging data including videos on how macrophage Nrf2 mediates the response to reactive oxidants during immunity, neuroinflammation, apoptosis and ageing. Menna El Gammal from Dr Fisun Hamaratoglu Dion lab at Cardiff University presented her PhD studies on the cell elimination strategies that occur during identity loss in the developing wing disc. Studying apterous (from the Greek word for without wing) mutant clones in the wing disc she characterised the mis-specified cells. To capture the underlying molecular changes, laser microdissection was used to cut out the clones for RNA-seq. Comparing loss and gain of function clones of the candidate genes identified to be up or down regulated she homed in on dLMO (a negative regulator of apterous) and Tau. Hannah Jones (Dr Giorgio Gilestro’s lab, Imperial College) switched from development to sleep, exploring the behaviour through time series analysis in order to screen insecticides and novel genes. She has adapted the ethoscope for video tracking sleep to a medium throughput microtitre plate format allowing screening of the effects of panels of insecticides at different doses using sleep. She found that most had a predictable effect and were effective at the lowest concentration added. She also presented some work on sleep rebound.
After tea and coffee, Jana Soenksen from Dr Benjamin Housden lab at the University of Exeter moved on to discussing disease modelling and the functional analysis of diabetes associated genes identified from GWAS. Apparently 8% of the world’s population have Type 2 diabetes which costs for instance 10% NHS budget. Jana has set up assays to study insulin receptor signalling and glucose uptake in flies and is screening through candidate genes that were identified by GWAS. She does this using RNAi against the fly homolog expressed in fat body versus the insulin peptide secreting neurons. She found that like in human, being raised on high sugar diet and during ageing you are more likely to get phenotypes. She hopes in future to screen for new treatments for these phenotypes. Last of all Dr Adam Bradlaugh from Prof. Richard Baines lab at University of Manchester discussed the essential elements of radical pair magneto-sensitivity. He described how Drosophila like other species are able to detect changes in magnetism, and that the blue-light photoreceptor and clock gene, Cryptochrome is important for this process. He discussed how FAD photochemistry as well as PDZ domains in the C-terminus of Cry may play a role in magnetic field sensitivity using whole cell patch clamp recordings from fly neurons. Many questions were asked, and future directions discussed and new contacts made afterwards over pizza and drinks kindly provided by the Genetics Society.
12th SWFM // 17 November 2021
The twelfth South-West Fly meeting was on 17th November 2021.
After a break over 22 months due to Covid, it was great to be able to be back at University of Bristol on the afternoon of 17th November for SWFM discussing the latest Drosophila research. Veteran SWFM speaker and supporter, Professor Helen White-Cooper of Cardiff University discussed the latest tools, sequencing, and expression data available through next generation sequencing, AI, web tools with curation from the expert fly community. More specifically the talk was on the FlyCellAtlas: What can you learn from chopping adult flies into little bits and then sequencing RNA from their nuclei. Helen gave a live workshop on the free online tool, so everybody can interrogate the expression pattern of their favourite fly gene or tissue namely the testis for Helen. Next Dr Edgar Buhl spoke about a new project he is researching at Bristol University with James Hodge, human geneticists and paediatricians using flies to model rare childhood neuropathies. Essentially the Bristol Children’s Hospital clinicians see a lot of kids with rare genetic diseases, which they have no idea what they are or how to treat them. As a means to diagnosis, treatment and understanding the disease, they are now sequencing their patients, and then the group make the equivalent mutation in the fly gene and looking for resulting neuropathic defects. The group has also started the first gene therapy in Bristol, for diseases like Amyloid Lateral Sclerosis. Continuing on the fly disease modelling theme, Eilish Mackinnon from Dr Owen Peters’ lab at the Dementia Research Institute at Cardiff University (DRI@CU) talked about the glial role of small wing/PLCG2 in modifying amyloid-associated phenotypes in Drosophila. This was an elegant set of PhD thesis experiments where a human gene identified by GWAS for Alzheimer’s disease (AD) performed by DRI@CU was knocked down in flies yielding AD-like effects of shortening life, eye degeneration and climbing defects. Many of these phenotypes were brought about through changing human amyloid processing. Strikingly phenotypes were due to misexpression in glia as opposed to neurons, with microglia now being thought to be key culprits in the progression of AD pathology. In fact, correcting small wing expression could rescue secreted human amyloid b defects. Eilish has just used CRISPR to make a conserved PLCG2 AD mutations into the fly small wing gene. Although humans don’t have wings and flies don’t get Alzheimer’s disease, ingeniously, the Cardiff group can monitor neurodegeneration live in the fly wing as well measuring any associated axonal trafficking defects by imaging GFP in the long sensory neurons of the fly wing in AD model flies.
After a tea and coffee break, Dr Paul Langton from Professor Eugenia Piddini’s lab at the University of Bristol talked about the role of Xrp1 and proteotoxic stress in Minute cell competition. He introduced the concept of winner and loser cells in terms of their growth, and importance in stem cell division as well as increased cell competition of cancer cells. His work takes advantage of clonal analysis in flies and ability to image live, count and measure the size of cells in developing discs. This allows you to study lethal genes, cell autonomy and boundary effects. Orthologues were looked at in human cells lines and manipulated pharmacologically. The last talk was from a recent postdoc, Dr Meg Stevens of Dr Benjamin Housden’s lab at the University of Exeter. They have been identifying novel drugs to treat neurofibromatosis type 1 tumours using combinatorial or synthetic lethal screening in Drosophila cells. This has involved performing a range of genetic and drug screens in the context of different diseases using Drosophila and human cells, using CRISPR to make analogous mutations in the genes of the two species. Drugs tended to translate well between the models, although there are challenges and differences of feeding the flies the drug as opposed to the cell cultures let alone finding the effective dose and treatment regime in a whole mammal. The high throughput capability and genetic tractability of flies will hopefully be leading to us being able to find more effective treatments in the future. It was great to be able to continue the discussion of fly research in person for the first time in nearly 2 years, and over pizza and drinks generously provided by sponsorship by the Genetics Society, the next meeting is 9th March, 2022, please email james.hodge@bristol.ac.uk if you want to be added to the SWFM special interest group and attend future meetings.
11th SWFM // 15 January 2020
The eleventh South West Fly meeting was held at University of Bristol on Wednesday 15 January 2020.
Dr Bilal Malik from Dr. Owen Peter's lab at Cardiff University discussed his screen for genetic modulation of autophagy in Drosophila. Autophagy is when damaged cellular products in membrane bound vesicles get digested in organelles. Defects occur in neurodegenerative diseases. Bilal discussed his work screening chromosome 3L for EMS induced mutations that cause autophagy defects. This was done by live imaging of glutamatergic axons in the adult wing with MARCM clones to restrict expression. Some interesting candidates were discussed and their parallel effects on mitochondrial dynamics and axon fragmentation high-lighted. The next talk was on the differential contribution of schizophrenia-related gene RIM to adult Drosophila behaviour by Sergio Hidalgo from Dr James Hodge’s lab at the University of Bristol. Sergio presented his thesis work, which explores the high heritability of schizophrenia including characterising mutations in a number of calcium signalling and neurotransmitter release regulator genes. He showed the RIM presynaptic vesicle trafficking molecule was important for olfactory behavioural, social space paradigm, circadian rhythms and neuropeptide release. Phenotypes also associated with the disease. Some the schizophrenia associated calcium channel mutants were also shown to have defective synaptic plasticity and memory in flies. After tea, the role of stress signalling in adult fly intestinal regeneration was discussed by Dr Parthive Patel from the University of Bristol. He showed that stem cells in human and fly intestine are similar allowing him to use flies as a high through put system to test the effect of ingestion of various stressors such as bacterial infection, reactive oxygen species, detergents and DNA damage. He showed that the JAK/STAT and MAPK pathways were upregulated replacing the damaged intestinal cells by increased intestinal stem cell proliferation. Over-proliferation and these pathways have also been implicated in cancer. The signalling molecules involved in responding to pathogenic bacteria were compared to those involved in immunity. Everyday ends with sleep as did this one, with a talk by Hannah Jones from Dr Giorgio Gilestro’s lab at Imperial on the modulation of sleep homeostasis by internal states. She demonstrated that sleep has two components, one circadian, e.g. when we sleep and one that is homeostatic, e.g. how much we sleep, as exemplified by the need for sleep, after you miss a night’s sleep. Hannah explored sleep deprivation (SD) in flies, by either starving the flies or housing them with members of the opposite sex. She discovered that males and females and even mated versus virgin flies respond differently in terms of their sleep rebound. She also incorporated arousal into her behavioural assays and was introducing the concept that there may be the concept cell fitness in the cells which remain in the brain after SD. By the end of the talk everybody’s internal state was saying, pizza and drinks which were generously provided by the Genetics society. The next meeting is 6th May at Biomedical Sciences Building, University of Bristol, please contacted james.hodge@bristol if you would like to attend.
10th SWFM // 9 October 2019
The tenth South West Fly meeting was held at University of Bristol on Wednesday 9 October 2019.
The first talk was entitled “A tunable genetic screening system and its application to the discovery of synergistic drug combinations” and was by Dr Benjamin Housden from University of Exeter. His lab has been performing elegant synthetic lethal drug and genetic screens for pathways involved in cell division and cancer using flies. Eva Daniela Ruiz from Dr. Amritpal Mudher's lab at the University of Southampton then discussed her thesis work on the biochemical and biophysical characterization of conformationally distinct tau protein species and their relationship with neuronal dysfunction in two models of tauopathy, comparing her fly models to a mouse model of tauopathy. Next speaker, again from University of Southampton was Dr Herman Wijnen who switched topic from Drosophila melanogaster to suzukii, discussing the work of his recently graduated PhD student, Beth Shaw on leveraging behavioural rhythms for integrated pest management of the spotted wing fly, which has started to geographically spread, causing wide spread damage of soft fruit crops. After tea, again on the topic of food security, Kiah Tasman from Dr James Hodge lab at the University of Bristol, talked about the effect of neonicotinoid pesticides on circadian rhythmicity and sleep in Drosophila and bumblebees, she also showed that field relevant doses of the EU banned insecticides removed fly memory. Last of all was a talk on cell elimination strategies during development by Dr Fisun Hamaratoglu Dion who has just set up her lab at Cardiff University. She discussed her work on cell-signalling in control of growth and cancer including using clonal mosaic analysis of wing discs, discussing the role of different signalling pathways in different compartments with lots of pretty pictures. Discussion of all things fly continued over refreshments kindly provided by the Genetics Society. Please contact james.hodge@bristol.ac.uk or visit http://www.genetics.org.uk/events/fly-south-west/ for more details. The next meetings are Wednesday 1:30-5:30pm on 15th January 2020 at Biomedical Sciences Building, University of Bristol.
9th SWFM // 8 May 2019
The ninth South West Fly meeting was held at University of Bristol on Wednesday 8 May 2019.
The first talk was entitled single-cell molecular cuisine in the fly brain by Dr Vincent Croset from Prof. Scott Waddell’s lab at the University of Oxford. They have been performing single cell sequencing to understand molecular changes underlying thirst and memory in flies. They found thirst modulates gene expression in glia via oxidation, metabolic and lncRNA pathways including through signalling involving a gene they called thirsty 1, whose knockdown decreases drinking in thirsty flies. Next, Dr Joaquín de Navascués of Cardiff University spoke about a (not so) simple bHLH network controls self-renewal and biopotential differentiation in the adult fly gut. His lab study intestinal stem cells and they showed emc seems to work in parallel to Notch which maybe upstream of daughterless. They also suggest bHLH interacts in bi-potential stem cells via E-box sequences such as GATA. After tea, there was an entertaining talk on structure-activity relationships of cryptochrome mediating magnetoreception by Dr Adam Bradlaugh from Prof Richard Baines’ lab at the University of Manchester. Adam discussed how the clock gene Cry may help animals like flies respond to magnetic fields. He suggested one theory was via a radical pair mechanism involving alignment of electrons in Cry’s FAD domain. He looked at the electrophysiological and circadian behavioural response of Cry mutants to magnetic field and different wavelength of light stimulation. Finally, Dr Giuliana Clemente from Dr Helen Weathers’ lab at the University of Bristol spoke about how Collagen-IV filaments guide and facilitate macrophage migration in Drosophila embryos. Giuliana talked about the role of Drosophila haemocytes which are equivalent to mammalian microphages in immune surveillance and developmental changes underlying hemocyte migration. She showed hemocytes follow collagen rich tracks during lateral migration and integrins are required to recognise these Collagen-IV bundles. Discussion of all things fly continued over refreshments kindly provided by the Genetics Society and SLS and continued in the pub. Please contact james.hodge@bristol.ac.uk or visit http://www.genetics.org.uk/events/fly-south-west/ for more details.
8th SWFM // 30th January 2019
The eighth South West Fly meeting was held at University of Bristol on Wednesday 30 January 2019.
The first talk was on how insulin resistance exacerbates tau pathology in Drosophila tauopathy models and neuroblastoma cell lines and was given by Dr Shreyasi Chatterjee from Dr. Amritpal Mudher's lab at the University of Southampton. Using the Drosophila eye, she performed a modulatory screen and found that chico (IRS insulin receptor) rescued the neurodegeneration caused by overexpression of Alzheimer disease (AD) associated human Tau 2N4R. Loss of function of chico (IRS) insulin receptor also caused increased fly sugar and lipid levels with insulin signalling molecules like GSK3Beta increasing phospho Tau so combining the signalling of AD and type 2 diabetes. Next up, Terrence Trinca from the Dr Joaquín de Navascués lab, Cardiff University lab spoke about his PhD project which was to create a Drosophila model for chronic radiation injury. >50% of cancer patients get radiotherapy, and then get late or chronic effects of the treatment, Terrence wants to find the genes involved in the process and has located an effect of the response to the gut.
Dr Benjamin Housden (University of Exeter) gave an interesting talk about his lab’s efforts to accelerate drug discovery using Drosophila screens. He proposes a novel approach of adding a fly RNAi cell-based screen before the normal human cell screening which precedes mouse studies and human trials, his results with TSC1 and 2 mutants suggest this decreases the rate of attrition through the drug target and development pipeline. He also proposed a new screening approach measuring changes in expression of gene targets using GFP, this allows you to look at gradient effects as a surrogate of dose response analysis. After tea, Dr Herman Wijnen from University of Southampton talked about light-induced plasticity of Drosophila central and peripheral clock function. They asked what were the longest and shortest day lengths the fly clock could keep up with? and found this was days of about 21hrs of light then 21hrs of dark and 7.6hrs of light and dark respectively. They determined the clock neurons and genes involved in the extremes of entrainment. The last talk was on investigating a mitochondrial role for Kynurenine 3-monooxygenase (KMO) by Dr Daniel Maddison from Prof. Flav Giorgini’s lab at Leicester University. He studied kynurenine pathway metabolism and its interaction with the mitochondrial proteins, Pink and Parkin. He showed he could rescue PINK1 and Park nulls with fly or human KMO and the interaction with a number of genes using an elegant blend of fly genetics, human cell culture and biochemistry. Discussion of all things fly continued over refreshments kindly provided by the Genetics Society and SLS and then continued in the pub. The next meeting is on 8 May please contact james.hodge@bristol.ac.uk or visit http://www.genetics.org.uk/events/fly-south-west/ for more details.
7th SWFM // 7th November 2018
The seventh South West Fly meeting was held at University of Bristol on Wednesday 7 November 2018.
The first talk was on how cold-induced period transcription links environmental temperature to the Drosophila molecular clock and was by Dr Akanksha Dafna from Dr Herman Wijnen lab at the University of Southampton. She showed it was possible for flies to entrain their clocks to 2-3oC temperature cycles (TC) in constant darkness (DD). The period clock gene was found to be better at resetting than timeless. They then performed a RNA-seq screen to see which transcripts changed their expression in these flies and looked for which parts of the promoter region of the period gene driving luciferase expression were required to respond to temperature entrainment. Next, Dr Paul Hartley from University of Bournemouth gave an interesting talk on studying aspects of human cardio-renal physiology using Drosophila. He went through the development of the fly heart and its potential to model human cardiac function showing a beautiful video of the fly heart. He showed that the fly nephrocytes and cardiac cells interacted with each other and could rescue mutant defects in one another.
After tea, Dr Roberto Feuda from the University of Bristol spoke about a common neurogenic toolkit in Bilateria. He discussed how the the nervous system may have evolved comparing the expression of a network of neurogenetic regulatory genes expression patterns in the urchin, snail and Drosophila. He showed that 87% of neural genes in urchin were also in Drosophila, however there are only 6 neurons in urchins and 100,000 neurons in flies. Dr Benjamin Kottler from Dr Frank Hirth’s lab at KCL talked about the inverse control of turning behaviour by dopamine D1 receptor signalling in columnar-wedge and ring neurons of the central complex in Drosophila. He showed how video tracking using the DART system could be used to study motor action selection in Drosophila, this was shown to involve the central complex region of the brain, the FoxP gene and dopamine signalling.
As all days begin with circadian rhythms and end with sleep, likewise the meeting started with a talk on circadian rhythms and ended with one on sleep. Dr Alice French from Dr Georgio Gilestro’s lab at Imperial discussed stimulus valence and arousal from sleep. She showed that some odours are more arousing than others, and that this could be studied using the Ethoscope computer tracking system and delivery of different concentrations of vinegar odour during sleep and watching how arousing the odours were. She found that 5% acetic acid was attractive and 10% aversive, however starvation could make even 10% acetic acid attractive. She then dissected the neuroanatomy of how the odours interacted with sleep and how the flies could switch their valence. Discussion of all things fly continued over refreshments kindly provided by the Genetics Society and SLS and continued in the pub. The next meeting is on 30 January please contact james.hodge@bristol.ac.uk or visit http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/ for more details.
6th SWFM // 13 June 2018
The sixth South West Fly Meeting was held at the Biomedical Sciences Building, University of Bristol on Wednesday 13 June 2018. Dr Angelique Lamaze (Dr James Jepson’s lab) (UCL) spoke about the circadian integration of environmental changes in Drosophila. She looked at the longest sleep bout response of flies after exposure to 30oC and showed the response was clock dependent and mediated by TrpA1 and Dorsal Neuron posterior (DN1p) clock neurons. Using a range of opto/thermo-genetic approaches she found the DN1p projected to the Anterior Optic Tubercle and noted that the flies’ day and night sleep were very different. Dr Owen Peters (Cardiff University) spoke about his lab’s work on the functions of conserved Alzheimer's Disease (AD) risk genes in the Drosophila nervous system. He compared the effect of overexpression of human AD causal genes with RNAi mediated loss of function of fly orthologs of a number of AD risk genes nominated from GWAS performed at Cardiff Dementia Research Institute (DRI). They compared the effect of neuronal and glia misexpression of the genes, measuring lifespan, neurodegeneration, locomotor and ERG electrophysiological defects. Another freshly minted DRI lecturer, Dr Gaynor Smith spoke about the genetics of axonal mitochondrial biology, this process is fundamentally important but also relevant to Parkinson’s disease (PD) which is associated with a range of mitochondrial genes and defects e.g. Pink and Park PD genes controlling mitochondrial fission. Harnessing the power of Drosophila forward genetic screens, she imaged mitochondria in wing neurons with OK371-Gal4>uas-tomato, uas-mito-GFP and performed a MARCM based embryonic lethal screen using Next Generation Sequencing to identify mutants with interesting mitochondrial phenotypes. She went to identify some of her hits, performed genetic rescue and verified results with orthologues in human cell culture.
Dr Katia Jindrich from Prof Helen White-Cooper lab at Cardiff University described her cutting edge molecular biological characterisation of non-canonical nucleosome positioning in Drosophila testis. Is the latest MNaseSeq she set out to map nucleosome positioning in wildtype and Meiotic arrest mutant testes, find 816 genes that lost their expression which is following up on. Jack Curran from Dr James Hodge lab at University of Bristol spoke about his thesis work using Drosophila to determine the effect of ageing on circadian rhythms and sleep. He showed like humans, flies have progressively weaker and longer rhythms as they age and this was accompanied by more sleep and change in clock neuron excitability and structural plasticity. He also performed a screen of rhythmically expressed clock neuron ion channels revealing specific effects on circadian rhythms and sleep. He has therefore elucidated key components of the mysterious membrane clock which can be considered future targets for treatments for ageing insomniacs. Following on nicely from the earlier talks of the day, James Higham presented his work determining the effect of pathological isoforms of human tau associated with AD. James elegantly showed that like in AD, tau results in loss of fly memory, circadian rhythms and sleep. He showed that he was able to take clinically relevant drugs to reverse some of the hyperexcitability caused by neuronal expression of tau, using a clever combination of calcium imaging of memory neurons and pharmacology. He showed for the first time the effect of human tau on neuronal excitability of clock neurons which include increasing firing at night, thereby removing the circadian change in firing across the day, preventing the AD fly from sleeping at night.
5th SWFM // 4th April 2018
The fifth South West Fly Meeting was held at the Biomedical Sciences Building, University of Bristol on Wednesday 4 April. Katarzyna Sierzputowska from Drs Benjamin Housden and James Wakefield labs at University of Exeter spoke about an integrated analysis of the protein-protein interaction network of the conserved mitotic kinase, Polo. Using a combination of a high throughput luciferase plate assay screen and embryo GFP imaging, she went through her data so far and her proposed PhD screen and validation. From first year PhD to Professor, Prof Herman Wijnen from University of Southampton gave a talk about the conserved small GTPase Rho1 couples molecular clock circuits to daily sleep/wake behaviour. Again, using a trusty Drosophila screen of the DrosDEL collection for circadian rhythm mutants, his group identified Rho-1 mutant. Rho-RNAi expression in clock neurons caused loss of rhythms in continuous darkness and a collapse of the expanded clock neuron terminal day time phenotype. After tea, Dr Lori Borgal again from Prof James Wakefield lab at University of Exeter, gave a talk entitled “PP2A-B’ regulation of Asp influences stem cell specific spindle pole focusing”. Lori’s talk explored the relationship between phosphatases and kinases in mitosis again taking advantage of GFP live imaging and genetic tractability of the fly. Dr Marc Amoyel (University of Bristol) presented his recent work studying the interaction between cell cycle regulators and stem cell fate. Surprisingly, he finds that factors that control proliferation in stem cells are also required to maintain the stem cells' niche. Lastly, Dr James Hodge from University of Bristol spoke about his labs work on Drosophila models of Alzheimer disease (AD). Based on a recent Epigenome Wide Association Study for AD, they took the top hit which was in the ankyrin gene and made a Drosophila model. These flies like those that overexpress human amyloid b or microtubule associated protein, tau, cause shortened lifespan, locomotor deficits and short-term memory loss. After the talks, there was refreshments kindly provided by the Genetics Society and SLS, and Drosophila researchers continued to discuss their results, planned experiments and role of the fly in science and beyond. If you are interested in attending or presenting at this meeting please contact james.hodge@bristol.ac.uk.
4th SWFM // 8th November 2017
The South West Fly meeting brings together nearly 30 labs in the South West using Drosophila as a model for their research. This was the fourth meeting of the group on 8th November 2017, at the University of Bristol, which featured a series of cutting edge research seminars interspersed with scientific discussion over refreshments kindly provided by the Genetics Society.
The first speaker, Emily Churchill from Dr Michael Thom’s lab at the University of Plymouth talked about the consequences of plasticity, posing the question of how environmental conditions affect Drosophila physiology and copulatory behaviours? She found older males took longer to initiate copulation and that starvation decreased copulation length in a way that particularly affected females, presumably due to egg laying being very energetically demanding. She also looked at the effect of sperm competition i.e. the effect of another male being present and plans to look at the effect of fluctuations in temperature conditions within and between generations in collaboration with Dr Jon Bridle.
Next up, Mike Dinan from Professor Eugenia Piddini’s lab at the University of Bristol talked about his work investigating the cell biology of cell competition. He showed that usually fitter cells take over, however sometimes this maybe a bad thing when cancer stem or neoplastic cells take over. So, what makes you are a loser or winner? He posed this question by making clones in the wing disc i.e. making small patches of tissue null for a lethal gene like, minute which makes that patch of tissue lose a ribosomal gene, hence the cells becoming losers, and smaller in size. He then performed RNA-seq on these cells and found enrichment in JAK/STAT, JNK and Nrf2 pathways and showed overexpression of Nrf2 was sufficient to make you a loser. He is now going onto determine the effect of environmental conditions on cell competition.
After tea, Alex Hull from Dr Herman Wijnen’s lab at the University of Southampton talked about his PhD work that shows that developmental (CLK/CYC) inhibition uncouples the molecular circadian oscillator from circuit-level functions and behavioural output. He showed that the is not a developmental requirement for the period (per) clock gene to make a clock circuit that generates circadian rhythms in the adult, but there is, for the Cycle (cyc) clock gene. In addition to measuring the molecular clock and behavioural rhythms, he measured the extent of synaptic arborisation of the dorsal projections of the small lateral neuron ventral clock neurons. He found that the LAR tyrosine phosphatase was important for the circadian modulation of the arbor size and that you could get behavioural rhythmicity in constant red light, although the mechanism of this remains a mystery and the focus of future work in the lab.
Riding high on the three Nobel prizes this year for Drosophila circadian rhythm researchers, we had a second fly clock talk by Philip Smith from Dr James Hodge’s lab at the University of Bristol. Phil talked about his work on Drosophila clock neurons and how they might keep time by electrical currents. His worked suggests that the clock circuit may consist of many individual analogue clocks in each clock neuron which are formed by the molecular clock. However, his hypothesis is that the individual clocks are joined together and synchronized by an electrical or digital clock formed by ion channels in the membrane that control the rhythmic firing of action potentials and release of circadian neuropeptides in the clock circuit. He showed that the Shaw voltage-gated potassium (Kv) channel was expressed highly in the morning and the Shal Kv channel was an evening channel. He confirmed this with electrophysiological recordings of their individual currents from the clock neurons. He then went on to make a mathematical model to show how the membrane clock may work and discussed how introducing a human Kv9 channel with a mutation that causes essential tremor, caused the clock neurons to be hyperactive and the flies to have difficulty sleeping at night, nicely mirroring the symptoms in humans.
Last of all Professor Helen White-Cooper of Cardiff University gave an entertaining talk on how and why a defect in the RNA export pathway causes muscle degeneration. Helen is usually interested in sperm however one of her male sterile mutants which was in a gene called Nxt1 had a strange phenotype of making a banana shaped-pupae. Her lab performed RNA-seq on the pupae and found surprisingly that the ecdysone genes which are key to metamorphosis were not affected or likely involved in this phenotype. However, she did find the muscle staining of the Nxt1 mutant was severely affected. She found that there was a change in expression of abba and titin and showed muscle expression of abba rescued the Nxt1 null phenotype. The RNA-seq data also showed that genes with long introns were preferentially downregulated in the Nxt1 mutant, the significance of this finding was to be determined by future work in her lab. Discussion of all things fly continued afterwards with drinks.
For further details about the South West Fly meeting please visit http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/ or contact Dr James Hodge (University of Bristol, james.hodge@bristol.ac.uk).
3rd SWFM // 3rd May 2017
The South West Fly meeting brings together nearly 30 labs in the South West using Drosophila as a model for their research. This was the third meeting of the group at the University of Bristol, with a series of cutting edge research seminars interspersed with discussion over refreshments kindly provided by the Genetics Society. Dr Helen Weavers started the meeting discussing her work on the induction of wound protection and tolerance in fly embryos in the lab of Prof Paul Martin and Will Wood at the University of Bristol. Helen showed some beautiful live imaging showing the multiple steps involved in migration of haemocytes/macrophages to wounds and the subsequent repair process. The effect of different chemo-attractants, the experience of apoptotic cells, manipulation of cell signaling was discussed as well as a computational collaboration that harnessed the power of 3D automated cell tracking. Next up Dr Ben Longdon (University of Exeter) discussed his team’s work on virus host shifts in 50 different species of fly. Understanding the fundamental principles of how RNA viruses interact with their hosts is important given the effects of Ebola, HIV and SARS and flies get viral infections in all the same ways as humans. Ben described the results of his experiments where he injected 50 different species of flies with 3 different Drosophila viruses and then measured their virulence (how many flies killed in 24hours) and the molecular consequences of infections were determined by qRT-PCR and RNA-Seq. The next talk was on bHLH network regulation of intestinal stem cell self-renewal and differentiation by Aleix Puigin from Dr Joaquin De Navascues Melero’s lab at Cardiff University. Aleix described his thesis work using daughterless, notch, delta and escargo’s genetics and immunohistochemistry to understand the signaling hierarchies involved in regulating stem cells. Drosophila workers from farer a field are always welcome at the South West Fly meetings, and Oliver Barnstedt from Prof Scott Waddell at the University of Oxford gave a beautiful talk on how the Drosophila mushroom body output neurons mediate memory and are cholinergic. He described how the dopamine input, mushroom body and output neurons form a tripartite synapse that underwent presynaptic long term depression during learning. Using an elegant mix of genetics, behavior, optogenetics, immunohistochemistry and pharmacology he showed that the synapse signaled via nicotinic acetylcholine receptors. To round things up Andy Saxon from Dr Jon Bridle’s lab at the University of Bristol discussed his work on male reproductive success under fluctuating vs constant environments. Andy is interested in life history trade-offs and studies a tropical rain forest species of Drosophila found in Australia. One example of such a trade-off would be between males trying to mate the whole time but also not wasting their precious resources of sperm that can be up to 200 times longer than human sperm. He found that the flies’ reproduction varies with altitude and that flies do best at certain temperatures, like 25oC, the temperature Drosophilist’s set our incubators. However, flies did less well when the environmental conditions were variable, possibly highlighting further implications of climate change on the reproductive success of vulnerable species. Discussion of all things fly continued afterwards with drinks. For further details about the South West Fly meeting please visit http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/ or contact Dr James Hodge, University of Bristol - james.hodge@bristol.ac.uk
2nd SWFM // 1st March 2017
The South West Fly meeting brings together nearly 30 labs in the South West using Drosophila as a model for their research. This was the second meeting of the group at the University of Bristol, with a series of cutting edge research seminars interspersed with discussion over refreshments kindly provided by the Genetics Society. The first speaker was Dr Marc Amoyel who recently set up his lab at University of Bristol, he spoke about how social interactions control stem cell fate. His beautiful work uses the testes as a model system and employs MARCM to generate single cell lineages showing the importance of hedgehog, MAPK and insulin signaling in these processes. Second up was Dr Neil Pearson from Prof Pete Cullen’s lab at University of Bristol talking about Sorting Nexins (SNX27) and describing its in vivo role in planar cell polarity and neurodegeneration, potentially linking some of the mutant effects seen in flies (generated by CRISPR) to some disease phenotypes in humans. Next, Dr Ruth Archer from Prof David Hosken’s lab at University of Exeter, gave an entertaining talk asking “Do men matter?” this was addressed by her ongoing work on mating patterns and how they might influence the evolution of post-reproductive lifespan. Although female flies do not have a menopause their fertility does decrease with age seemingly at a different rate to males. Towards the end of the afternoon spent in a darkened lecture theatre Dr Edgar Buhl further convinced the audience of the importance of their inner body clock. He described a range of elegant studies he conducted in Dr James Hodge’s lab at the University of Bristol showing how environmental light and temperature affect the electrical ticking of the flies’ clock and how this outputs to behaviour. Remarkably the components and how they come together to form a molecular and membrane clock seem to be highly conserved with those in humans. To finish off Dr Andrew Davidson talked about his work on how macrophages combine chemotaxis with phagocytosis performed in Prof Will Wood’s lab at the University of Bristol. He showed a series of very impressive movies of moving haemocytes with fluorescent cytoskeletons and with mutations in Scar, Wave, Ena and Dia. Andrew showed the importance of these molecules in immune surveillance, UV induced apoptosis and wound recruitment and found that even in flies, there is redundancy requiring multiple genes to be hit before these vital tasks are compromised. Discussion of all things fly continued afterwards over drinks. The next meeting will be on 3rd May 2017, for further details about the South West Fly meeting please visit: http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/ or contact Dr James Hodge, University of Bristol, Email - james.hodge@bristol.ac.uk
1st SWFM // 30th November 2016
The inaugural South West Fly meeting at the Biomedical Sciences Building, University of Bristol on 30th November, began with a talk by Dr Anna Franz from Prof Paul Martin and Will Wood labs at the University of Bristol on how motile fat body cells play multiple roles during wound healing. Anna presented her research on a novel class of cell performing systemic and local wound healing functions. A series of beautiful imaging mostly live showed that these massive cells move in a “Mr Blobby” fashion to plug up laser generated wounds in the flies epithelium. Next Jack Chen from Dr James Wakefield lab at the University of Exeter presented his work that used quantitative proteomics of Drosophila microtubule associated proteins to identify a role for the replication factor C complex in mitotic progression. Jack’s work reiterated the importance of Drosophila screens in the discovery of new gene function as well as the beauty of watching synchronized GFP labeled chromosomes undergoing mitosis in the syncytial embryo. After tea, Dr Simona Caporilli from Prof Helen White-Cooper’s lab at the Cardiff University spoke about the regulation of gene expression in testes and how flies make sperm. Simona showed us how the next generation of Drosophila screens have received a reboot courtesy of RNA-seq technology. Amazingly she found that about 10% of genes in the fly genome are only expressed in the sperm. Finally Dr Nicholas Priest from the University of Bath gave an entertaining talk on how flies drink alcohol to fight sexually transmitted infections. He showed us how flies can adaptively shift their diet choice, including becoming anorexic to reduce the intake of sugar, which results in lower microbe loads. His lab found that most Drosophila infections were transferred via copulation and a small amount of alcohol could stave off these sexually transmitted infections. So safe in the knowledge that a little of what you fancy can do you good: we continued our fly discussions over a glass of wine (or two). For further details about the South West Fly meeting please visit http://www.bristol.ac.uk/phys-pharm-neuro/events/fly-meetings/ and contact Dr James Hodge, University of Bristol, Email - james.hodge@bristol.ac.uk