In a few words: Student-centred development through training, demonstration, discussion and guidance
Provision of Training
Training is essential for the development and scientific growth, and it will always be available and provided by the most appropriate colleague (myself, Post-Docs, other academics, facility managers, other PhD colleagues) and within the established guidance for the safe practice. As time progresses and you become more confident, you will be given an opportunity to train undergraduate and postgraduate students working on their projects within the team. In the early months of your PhD you will in parallel train your laboratory skills and go through literature review to familiarise yourself with the topic of your PhD research. As you become more experienced and confident with your time management, you will have more freedom to organise your work schedule according to the research needs whilst in-line with your other commitments.
Progression and Monitoring
Within the first months of your PhD I will be available on the daily basis and we can plan your timetable together in both formal and informal setting. We can set timetabled meetings to discuss progress and project management (usually weekly). We can include other academics in scheduled meeting if needed. In the early days, you will benefit from my scientific input, but as you evolve ad a researcher I expect you to take ownership of your research. This doesn’t mean that my support will become less available, rather than it will become more a discussion and collaboration between colleagues. I will always be there for support and additional guidance.
Work-Life balance is essential to your wellbeing and I will support you in trying to achieve this. Our communications will mostly be face to face, in person through an Open Door policy and through regular meetings. We use a TEAMs channel for routine communications within the group. I will be available and happy to provide additional support as required and within my means to secure your development as an early career scientist.
PhD Students can expect scheduled meetings with me:
In a group meeting
At least once a month
In year 1 of PhD Study
At least once a week
In year 2 of PhD Study
At least once a week
In year 3 of PhD Study
At least once a week
These meetings will be mainly face to face, and I am usually contactable for an instant response on every working day.
Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.
Notice Period for Feedback
I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.
Dr Milic is the primary supervisor on the below project:
Defining a role for extracellular vesicle-mediated sphingolipid signalling and crosstalk with the immune system
Secondary Supervisor(s): Dr Mariaelena Repici
University of Registration: Aston University
BBSRC Research Themes: Understanding the Rules of Life (Immunology)
Control of the immune system activity is crucial to the maintenance of health, regenerative responses in healthy ageing but it also plays a role in the induction of disease when controlled poorly. Macrophages are a key immune cell that controls pro inflammatory and anti-inflammatory responses and by doing so are crucial cells for the maintenance of health and homeostasis. The phenotype of macrophages can change in response to their microenvironment and extracellular vesicles (EV) appear able to control this phenotype but the mechanisms remain poorly defined. Intercellular communication mediated through extracellular vesicle (EV) release is only recently acknowledged as a novel mechanism of cellular crosstalk1. Because of their diverse biomolecular cargo, EV are capable of transmitting complex instructions to the recipient cells beyond the ‘classical’ soluble factor signalling.
Our previous research suggests that EV are metabolically-active extracellular compartments, rich in bioactive lipid mediators of inflammation and active enzymes responsible for their synthesis2. Such EV may act as extracellular messengers capable of modulating immune responses in recipient cells and tissues. Our work shows that the balance between the carried enzymes and their bioactive products within EV may determine the outcome (‘activation’ or ‘silencing’) in the recipient cells of the immune system, such as macrophages. Why is this important? Understanding how this balance of enzymes and bioactive lipids maintains health and is altered in disease and communicated in the surrounding tissues will highlight the importance of EV-mediated signalling in both health and disease.
Our recent work identified an intact sphingolipid enzymatic pathway in EV isolated from brain tissue, a pathway known to play an important role in inflammation. Sphingolipids are integral components of cell membranes with bioactive properties involved in regulation of many aspects of cell fate and function3. These lipids, as well as the enzymes responsible for their biosynthesis, are highly enriched in the central nervous system where they regulate a variety of cellular processes in physiological and pathophysiological conditions. We have also identified that brain-derived EV are enriched in different sphingolipid classes, with both pro-inflammatory and anti-inflammatory properties. However, to date, the role of bioactive sphingolipids and enzymes responsible for their synthesis in EV-mediated immunomodulation within the central nervous system remains ill-defined.
This innovative research proposal aims to understand the balance of these enzymes and bioactive lipids in EV in healthy and pathological brain and how this may be altered to promote either neuro-inflammation or tissue homeostasis. The fundamental nature of lipid signalling will further pave the way to a better understanding of neurodegenerative disorders and will define potential novel targets for future therapeutic approaches.
To answer these questions, this project will use a broad range of bioanalytical techniques including cell culture, nanoparticle isolation and analysis, mass spectrometry and data analysis, protein biochemistry, enzyme activity assays, flow cytometry and assays of immune cell function and inflammation.
1 Van Niel, G., D’Angelo, G., & Raposo (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews: Molecular Cell Biology: DOI: 10.1038/nrm.2017.125
2 Grant, L., Milic, I. & Devitt, A. (2019). Apoptotic cell derived extracellular vesicles: structure-function relationships. Biochemical Society Transactions: 47(2): 509-516.
3 Verderio, C., Gabrielli, M., Giussani, P., (2018) Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles, J Lipid Res, 59(8),1325-1340.
- Mass spectrometry of lipids and proteins: to profile and relatively quantify lipid and protein profiles of cells and derived EV with a focus on immunomodulating enzymes
- Cell culture: Cell culture of a range of cell lines and primary cells for the isolation of EV, isolation of primary cells from human peripheral blood for the immune-system crosstalk functional studies.
- Vesicle analyses: isolation and analysis of EV structure and function using Exoid tenable resistive pulse sensing, nano flow cytometry, analysis of immune-modulating capability in vitro using established functional assays.
- Imaging and analysis: Flow cytometry, Confocal microscopy, automated cell imaging for functional studies
- Protein biochemistry: Western blotting, Cytokine assays, Enzyme activity assays