Wilson Group

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.