Exploring cellular calculation with the B lymphocyte model
Project type
Honours
| Supervisor(s) | Division | |
| (Primary) | Immunology | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Immunology | .(JavaScript must be enabled to view this email address) |
Details of project
The naïve B lymphocyte is a type of stem cell, capable of self-renewal and following many different possible differentiation paths that play an essential role in successful antibody responses. For this reason the B cell is an excellent model for studying the interplay of receptor delivered signals and how they affect cell behaviours such as division, death and differentiation simultaneously.
Exciting recent advances mean we can follow cell lineages using video microscopy and detect fluorescent indicators for times to divide, die and change cell types. We will also use a new fluorescent mouse model, FUCCI, to follow the exact times of cells in different phases of the cell cycle following stimulation (in vitro) or immunization (in vivo).
In this project we will use these methods to measure B cell behaviours under different conditions. We will ask how known B cell modulating cytokines (IL-4, IL-5, interferon-gamma, TGF-beta) simultaneously affect cell division times, death times and frequency to isotype switch (IgG1, IgG2a, IgE) and become plasma cells. The student will also work with bio-mathematicians to build simulations and models based on their discoveries. Predictions will be tested both in vitro and in vivo.
Our goal is to understand the rules of cell behaviour well enough to predict the immune response and manipulate the outcome rationally. This work will attain an important step toward realising this goal.
Research interests
The immune system has fascinated scientists for decades. On the one hand it appears immensely complex, involving the coordinated contribution of many cell types. However, when cells are studied in isolation they follow clear simple rules suggesting a comprehensive theory is within reach of science - especially given the powerful array of present day tools for cell exploration and data gathering.
Our laboratory is interested in the regulation of the many directions the immune response can take, both in responding to infection, and when ‘getting it wrong’ during autoimmunity or allergy. To explore this question the Hodgkin laboratory combines experiment with theory and quantitative mathematical modeling. We have developed new techniques for studying the ongoing immune response and the changing patterns of response mediated by combinations of different signals. We are also attempting to develop powerful new tools for direct imaging of cellular responses.
Over the last decade we have developed an understanding of lymphocytes as following fundamentally simple behaviour but with the complication that an extraordinary degree of randomness arises from their ‘construction’, effectively making every cell different. Models that capture this random element using probability distributions are capable of powerful predictions of the immune response. We will apply this framework to address the specific research projects outlines below.
Research theme
Infectious diseases
Scientific discipline
- Autoimmunity
- Immunology
- Mathematics
- Systems Biology