Drosophila male secondary cells provide a unique system to track and genetically dissect the evolutionarily conserved maturation events of regulated secretion in real-time
Genetic manipulations that induce Alzheimer’s Disease appear to disrupt these maturation events in secondary cells, generating phenotypes that mirror the earliest defects observed in patients
Secondary cells make a new class of evolutionarily conserved exosomes that reprogramme female behaviour after mating and transmit specific signals from cancer cells
Secondary cells share many similarities with human prostate epithelial cells
Secreted microcarriers are neutral lipid-based structures that store and disperse key signals in reproduction
Regulating Secretion of Proteins, Exosomes and Microcarriers: Fundamental Processes Disrupted in Alzheimer’s Disease, Cancer and Other Human Diseases
We study the mechanisms by which cells package, secrete, store and dissipate signalling molecules and how these mechanisms affect physiological processes, such as growth and reproduction, and malfunction to promote aberrant signalling and cellular degeneration. We use a unique cellular model in flies in which we can visualise the internal assembly of regulated secretory compartments for the first time. We have discovered multiple highly conserved maturation events in secretion that are disrupted by genetic manipulations implicated in major human diseases and we are beginning to identify pathways that could be targeted to suppress these defects in potential therapies.
Our primary research questions
In multicellular organisms, cell-cell signalling plays a critical role in development and adult homeostasis, co-ordinating tissue and organ function. Traditionally, we consider secreted signals as single molecules, but it has become increasingly clear that they often function within multimolecular complexes. For example, they may be assembled in so-called dense-core granules (DCGs) inside secreting cells or associated with extracellular vesicles and other lipid-containing structures. Exosomes are extracellular vesicles made in intracellular endosomal compartments, which are then secreted to mediate complex physiological signals, when these compartments fuse with the plasma membrane. In flies, we have shown that exosomes in seminal fluid can normally reprogramme a female’s behaviour, so she rejects other males who approach her. Defects in the production of signals are implicated in the pathology of several major human diseases, such as cancer, diabetes and neurodegenerative disorders. For example, in cancer, exosomes are thought to pass through the circulation and reprogramme normal target cells, so that they form a new niche for metastasis, while in Alzheimer’s Disease (AD), there is increasing evidence exosomes interact with Aβ-peptides, which form extracellular amyloid plaques.
But how are complex signalling assemblies formed and their secretion regulated? Our understanding in this major field of modern cell biology remains surprisingly limited, primarily because the dynamic assembly events inside secretory compartments can typically only be visualised in fixed cells using electron microscopy. We have developed a new and unique genetic model in Drosophila, the fly accessory gland. One prostate-like cell type in this gland, the secondary cell, contains compartments that form both DCGs and exosomes and are thousands of times larger than in other animal cells, allowing us to follow compartment maturation by fluorescence microscopy for the first time in living tissue.
Combining this approach with inducible, cell type-specific genetic manipulations, we have been able to address several key questions in the field, showing:
Secretory compartments require input from recycling endosomes to mature and generate a DCG and exosomes;
Protein aggregation in DCG biogenesis is membrane-dependent, involves Amyloid Precursor Protein (APP), a key player in AD, and is disrupted by genetic manipulations that induce neurodegeneration in AD (Singh et al., 2025);
Exosomes with unique physiological and pathological functions are generated in recycling endosomes, so-called Rab11-exosomes, in addition to late endosomes, a conserved process from fly to human;
Formation of these exosomes is intimately linked to DCG biogenesis, and
Secreted proteins can also be stored in lipid-containing structures called microcarriers that rapidly dissipate in the female reproductive tract to trigger signalling.
Our research objectives
![]() |
1. To understand the mechanisms by which Rab11-exosomes and other extracellular vesicles are generated and secreted, and how each exosome subtype mediates its specialised functions; |
![]() |
2. To characterise the regulatory steps that control DCG maturation, how these are disrupted by genetic changes involved in AD, and how to suppress the resulting defects; |
![]() |
3. To identify and analyse other extracellular multimolecular signalling complexes, such as microcarriers, which store signals and permit their dissipation near target structures; |
![]() |
4. To characterise the signalling mechanisms that control prostate cancer growth and secretion, using our Drosophila accessory gland model; |
5. To employ the Drosophila secondary cell to explore the mechanisms regulating other secretory and endosomal processes, and their links to diseases, such as endocrinological diseases and lysosomal storage disorders. Examples of such mechanisms are given in the links to the other four objectives. |
Why study the fly accessory gland?
The tools available in Drosophila make it arguably the most genetically versatile animal model in the field of cell biology. But tissues, cells and subcellular structures in insects are typically small relative to mammals. In the fly accessory gland, secondary cells are a remarkable exception with giant lysosomes and secretory compartments, which contain enlarged DCGs and intraluminal vesicles that are secreted as exosomes. Furthermore, the lumen of the gland is extremely large and fills with fluid in the first three days of adulthood, as the secretory epithelium develops and matures. It is this enlarged lumen that allowed us to identify microcarriers as a new form of signal storage.
The male accessory gland performs the equivalent functions to organs like the prostate gland and seminal vesicles in humans. We have shown that secondary cells in particular share properties with prostate cells. They continue to grow in adults under the control of a steroid receptor and secrete exosomes that fuse to sperm in the female reproductive tract. We continue to investigate the parallels with the human prostate and more recently have employed secondary cells to analyse the fundamental mechanisms that control secretion, enabled by the very large size of secretory compartments and exceptional fluorescent live-cell markers for DCGs, exosomes and endolysosomal compartments.
For many years, our group has used Drosophila to provide new insights into the evolutionarily conserved biology that underpins normal cell functions, eg. Goberdhan et al., 1999; Goberdhan et al., 2005. Our most recent work has opened windows to the study of several previously intractable and uncharted areas of secretory biology, see Wells et al., 2023; Singh et al., 2025 and suggests that further development of our understanding will have significant impact in several disease-related areas.
Interested in joining the group?
Whether you’re an aspiring undergraduate or graduate student, or an experienced researcher, who would like to use the accessory gland system to analyse a challenging cell biological question, we encourage you to contact us to find out more. You’ll have the opportunity to interact with our collaborators, working in evolutionary and population biology, biotechnology, and biomedical and clinical science.
In the lab
Wilson Group News
Key exosome subtype in cancer progression identified
8 March 2023
New form of gift wrap drives male reproductive success
26 January 2021
Probing the genetics of advanced prostate cancer in fruit flies
25 October 2019
Three new Professors in DPAG
16 July 2015
Lab Bulletin
HILARy 2023
COMING SOON
...Michaelmas 2017
- ...New BBSRC-funded, three-year postdoctoral and part-time technician positions to work on exosome regulation in flies and human cells
- August 2017: Warm welcome to Dr. Pauline Marie, who has started working in the group as a CRUK-funded postdoctoral researcher in collaboration with the Goberdhan group
- August: Warm welcome to undergraduate students Jedrzej Jaworski and Alan (Jialin) Liu, who have joined the lab for summer research projects
- August: Good bye to Dr Aaron Leiblich who will leave the lab again for six months to return to his medical work full-time
- July: Dr Clive Wilson hosts an Alumni evening at St. Hugh’s College for UNIQ summer students interested in studying the medical sciences as undergraduates
- July: Dr Clive Wilson presents some of the lab’s latest findings at the Gordon Conference on ‘Fertilisation and activation of development’, New Hampshire, USA
- June: Congratulations to 3rd year DPhil Student Ben Kroeger for winning the second prize at this year’s “Sherrington Talks and Poster Day”
- June: Good Luck to 3rd year DPhil students Josephine Hellberg and Ben Kroeger who are presenting their research at this year’s “Sherrington Talks and Poster Day”
- May: Warm welcome to Biomedical Sciences undergraduate student Isabelle Newell and Medical Sciences undergraduate student Nick Parkes who start their FHS projects in the lab
- April/May: Dr Clive Wilson presents different aspects of our research at the Regulation of Cell Death and Protein Degradation Symposium, New York and the 5th Drosophila developmental cell biology workshop, Scotland
Join the Group
Fellowship applicants
If you have an interesting idea of how to use the accessory gland system to address your research question, please get in contact. We would be happy to discuss possibilities to collaborate with you, providing training opportunities or facilities to develop your ideas.
Postdoctoral researchers
We periodically advertise for new postdoctoral research positions. If you have specific questions or interests, you are welcome to contact us.
Clinicians
Clinicians have worked in the group both as Training Fellows and in postdoctoral research positions. Our work provides fascinating opportunities to develop translational projects, and we have excellent collaborations with several academics in the Clinical School to progress these programmes. Please contact us for more details.
Graduate students
Graduate students have played important roles in developing our work on the accessory gland over the years. There are opportunities to join the group, either by bringing your own award or funding, or through the competitive UK and international graduate scholarship schemes in Oxford. Contact us with your specific enquiry to find out more.
Undergraduate students
We regularly host undergraduate students for short- and long-term projects, and welcome specific enquiries from interested students from the UK and internationally.
Related research themes
We dissect the molecular and cellular mechanisms ...
We study everything from the structure of ion ...
We use the full range of modern molecular genetic ...
We play a leading role in the development of more ...