Professor Corinne Smith

Supervisor Details

Contact Details

School of Life Sciences, University of Warwick

Scientific Background

Research Interests

Clathrin-mediated endocytosis allows cells to capture nutrients and other important molecules by engulfing them in a capsule made from the plasma membrane. This is a vital process that contributes not only to nutrient uptake but to other cellular functions including recycling of synaptic vesicles in the brain, communication within and between cells and development of cells and tissues to perform specialised functions. In addition the endocytic apparatus is used by some viruses (notably HIV and influenza) and bacteria to gain entry into cells and there is accumulating evidence that endocytic proteins are associated with a wide range of diseases including neurodegenerative disease and cancer.

Clathrin-mediated endocytosis operates through formation of a vesicle from the cell's membrane trapping cargo molecules inside. This process is controlled by a network of proteins which include clathrin and a set of adaptor proteins which bind to clathrin. Clathrin assembles to form a polyhedral cage which, together with its adaptor proteins, forms a coat around the vesicle. The vesicles then detach from the membrane and move to a location inside the cell to deliver their contents. It remains a mystery how so many different adaptor proteins coordinate with a single protein so that this cellular postal system can achieve its function.

We aim to solve this mystery using two main approaches. First, by using electron microscopy images of frozen protein mixtures we can determine three-dimensional maps that show what these proteins look like and how clathrin’s adaptor protein binding partners are arranged within a cage structure. Secondly, by using advanced biophysical techniques we can measure how these adaptor proteins bind to clathrin and how clathrin cage assembly and disassembly is controlled. In this way we hope determine how clathrin coats specify and are involved in so many critical functions in cells.

Scientific Inspiration

My scientific inspiration comes from the pioneering ethos of the lab in which I did my own PhD, summed up by the ambition to identify the key, ‘killer’ experiment and use enterprise, imagination and courage in equal measure to carry it out.

Research Groups

Corinne Smith Lab

Cells and Development

Warwick Analytical Science Centre (WASC)

Supervision Style

In three words or phrases: Supportive, collaborative and inclusive.

In the words of Sandy Schmid, who is another of my research heroes: ‘I try to create a laboratory environment in which everyone can be as successful as their own skills and efforts allow, in whatever direction their passion takes them.’

Provision of Training

I will support and advise you throughout your PhD. Your technical training will be supervised initially by my experienced post docs/PhD students. Once you are confident in the basic techniques, I will expect you to proactively seek out the training you need to develop your project and become an independent scientist.

Progression Monitoring and Management

We will discuss your progression on a weekly basis, taking into account your training requirements and career aspirations. If I have concerns about your progress we will always discuss a plan of action together.

Communication

We communicate both formally through regular group meetings and informally via WhatsApp, e-mails and popping into my office.

I am always happy to discuss any issues that are impacting your ability to fulfil your potential and obtain a high quality PhD.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per fortnight

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 4 of PhD study

At least once per fortnight

These meetings will usually be face to face, and I am usually contactable for an instant response on every working day.

Work Pattern

The timing of work in my lab is usually flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Dissecting the mechanism of clathrin-coated vesicle formation

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Dissecting the mechanism of clathrin-coated vesicle formation

Secondary Supervisor(s): Dr Nikola Chmel

University of Registration: University of Warwick

BBSRC Research Themes:

Understanding the Rules of Life (Structural Biology)
Integrated Understanding of Health (Ageing, Diet and Health)

Project Outline

Clathrin-mediated endocytosis is a fascinating mechanical phenomenon that drives the selective internalisation of molecules into cells. Nutrient uptake, synaptic vesicle recycling, signalling, determination of cell polarity and development all rely on endocytic mechanisms. In disease, viral and bacterial pathogens exploit endocytosis to gain entry into cells and malfunctions lead to tumour formation, neurodegeneration and heart disease. In order to work properly, clathrin-mediated endocytosis requires more than 20 adaptor proteins to form a coated vesicle which will be able to select molecules from the outside of the cell for delivery to specific destinations. Our aim is to understand how the proteins involved in the network of clathrin and its adaptor proteins interact to achieve clathrin-coated vesicle formation.

In this project you will use biophysical and structural biology techniques to visualise adaptor proteins binding to clathrin cages and to analyse the dynamics of those interactions. An example of one of these clathrin cage structures determined using cryo-electron microscopy is shown on the left (Morris et al 2019). The techniques used in this project may include high resolution cryo-electron microscopy, small angle neutron scattering, dynamic light scattering, time-resolved fluorescence anisotropy and surface plasmon resonance (SPR, Biacore). By combining results from this wide range of approaches we will be able to investigate how clathrin-adaptor interactions result in formation of a functional coated vesicle network. Access will be provided to the Gatan K2 Summit direct detector and Jeol 2200FS 200kV transmission electron microscope at the Advanced Bioimaging Research Technology Platform, the Titan Krios microscope available in Leicester through the Midlands Regional Cryo-EM Facility and excellent facilities for biophysical analysis available within Warwick School of Life Sciences. This is a fabulous opportunity to apply cutting edge techniques to discovering how clathrin and its adaptor proteins drive clathrin mediated endocytosis.

References

Smith SM, Smith CJ. Capturing the mechanics of clathrin-mediated endocytosis. Curr Opin Struct Biol. (2022) 75:102427.

Smith SM, Larocque G, Wood KM, Morris KL, Roseman AM, Sessions RB, Royle SJ, Smith CJ. Multi-modal adaptor-clathrin contacts drive coated vesicle assembly. EMBO J. (2021) 40(19):e108795.

Morris KL, Jones JR, Halebian H, Wu S, Baker M, Armache J, Ibarra AA, Sessions RB, Cameron AD, Cheng Y, Smith CJ. Cryo-EM of multiple cage architectures reveals a universal mode of clathrin self assembly. Nature Structural and Molecular Biology (2019) 26(10):890-898.

Investigating the use of novel nanoparticles to improve targeted drug delivery

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Investigating the use of novel nanoparticles to improve targeted drug delivery

Secondary Supervisor(s): Professor Stephen Royle

University of Registration: University of Warwick

BBSRC Strategic Research Priority:

Integrated Understanding of Health (Diet and Health, Pharmaceuticals)
Renewable Resources and Clean Growth (Industrial Biotechnology)
Understanding the Rules of Life (Structural Biology)

Project Outline

Lipid nanoparticles (LNPs) are key reagents in the delivery of therapeutic drugs and genes due to their biological compatibility and ability to encapsulate a wide range of molecules. Traditional LNPs, however, present challenges such as large size, which limits cellular uptake, and vulnerability to manufacturing processes. We are developing an innovative alternative to these traditional nanoparticles that addresses these challenges and has the potential to be directed to specific locations within cells and tissues. This is particularly important in cancer therapy but also has relevance to a wide range of therapeutic needs. This project aims to harness the unique properties of these nanoparticles in cells to facilitate targeted drug delivery by exploiting our recent advances in understanding endocytosis mechanisms.

This project will employ state of the art imaging techniques including live cell confocal microscopy, imaging flow cytometry and 3D electron microscopy of cells. Using these techniques you will track fluorescently labelled nanoparticles within cells to understand the cellular response they produce. You will then take part in designing and evaluating chemical modifications to these nanoparticles in order to improve their uptake into cells and the delivery of reagents to specific cellular locations. This is a fabulous opportunity to apply cutting edge techniques to the design and development of nanoparticles with therapeutic potential.

References

Smith SM, Larocque G, Wood KM, Morris KL, Roseman AM, Sessions RB, Royle SJ, Smith CJ. Multi-modal adaptor-clathrin contacts drive coated vesicle assembly. EMBO J. (2021) 40(19):e108795.

Ball LE, Riley LJ, Hadasha W, Pfukwa R, Smith CJI, Dafforn TR, Klumperman B. Influence of DIBMA Polymer Length on Lipid Nanodisc Formation and Membrane Protein Extraction. Biomacromolecules. 2021 Feb 8;22(2):763-772. doi: 10.1021/acs.biomac.0c01538.

Co-supervisor on projects with Dr Jeremy Keown and Professor Stephen Royle.

Previous Projects (2024-25)

Primary supervisor for:

Cryo-electron microscopy of plant clathrin cages

Co-supervisor on a project with Dr Antonia Sagona.

Previous Projects (2023-24)

Primary supervisor for:

Cryo-electron microscopy of plant clathrin cages Dissecting the mechanism of clathrin-coated vesicle formation