Dr Alba Llibre Serradell

Supervisor Details

Contact Details

Institute of Inflammation and Ageing, University of Birmingham

Scientific Background

Research Interests

Tuberculosis (TB) is a major global public health problem in which one in four of the world’s population is latently infected. Host-directed therapeutics, in which drugs target host-mediated responses to pathogens rather than acting directly on the pathogen, are an emerging and promising strategy. In order to develop this approach towards new drugs for TB, we urgently require a comprehensive understanding of how host-pathogen interactions impact cellular pathways to regulate the immune response to the pathogen and influence disease outcome.

Metabolic reprogramming is crucial for determining successful immune responses. It is now well known that infection with Mycobacterium tuberculosis (M.tb) induces a switch in cell metabolism to active glycolysis.

Through an interdisciplinary approach, combining the fields of clinical microbiology, immunology, metabolism and big data, Dr Llibre research focuses in answering the urgent question of how immune-metabolic responses impact the host’s ability to resolve M.tb infection. This knowledge has the potential to reveal new host immune-metabolic therapeutic targets for TB disease.

Supervision Style

In three words or phrases: inclusive, supportive, collaborative.

Provision of Training

During the first weeks I will take responsibility for the candidate's training to make sure they get confident and independent continued support and guidance will be provided, without micromanaging. We will discuss and agree strategies and boundaries, so that the candidate feels safe and motivated, as well as owner of their project, and equipped with the required technical skills.

Progression Monitoring and Management

The candidate will attend weekly (Llibre and Bhatt groups) meetings, where critical, constructive criticism, and full understanding and support of research challenges will be provided. I am committed to a positive research culture, an essential ingredient of research excellence and wellbeing of researchers, and we will work together to achieve the candidate's professional aspirations.

Communication

I am very approachable and very keen on establishing effective communication strategies with all the team members, as I believe this leads to happier researchers and high quality science. In person or via email (during yours and mine working ours), I'm happy to discuss both science and pastoral-related issues.

PhD Students can expect scheduled meetings with me:

In a group meeting	In year 1 of PhD study	In year 2 of PhD study	In year 3 of PhD study
At least once per week	At least once per week	At least once per fortnight	At least once per month

Meetings will be a mixture of face to face and via video chat or telephone, and I am usually contactable for an instant response on every working day.

Working Pattern

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 2 weeks' notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Investigating the dual impact of lactate on the pathogen and the host during Mycobacterium tuberculosis infection

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 dual impact of lactate on the pathogen and the host during Mycobacterium tuberculosis infection

Secondary Supervisor(s): Dr Apoorva Bhatt

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Immunology, Microbiology)

Project Outline

Tuberculosis (TB) is a public health challenge; in 2021, 10.6 million people fell ill with TB and 1.6 million died. The causative agent of TB is Mycobacterium tuberculosis (M.tb) and its primary target are lung macrophages. Multidrug resistant TB is a global health threat, and we urgently need new drugs to fight it.

Lungs of M.tb-infected hosts are lactate-rich environments. Lactate is an active signalling molecule and macrophages respond to it through different transporters/receptors. M.tb can use lactate as a fuel source, and to synthesise aminoacids. There has been a very strong selective pressure on the lactate dehydrogenase lldD2 gene, suggesting a key role for survival. Furthermore, lactate shapes mycobacterial transcription, resulting in changes in cell wall lipids and virulence factors.

We have a poor understanding of how lactate shapes macrophage responses to M.tb, and how it impacts mycobacterial fitness, both key factors that dictate infection outcome. Based on preliminary data, our working hypothesis is that lactate in TB lungs strengthens the macrophage’s ability to kill M.tb, and that modulating host and/or mycobacterial responses to lactate has therapeutic potential.

Aim

The overarching aim of this project is to investigate the impact of lactate on M.tb infection resolution by:

1. Dissecting the molecular mechanisms by which lactate drives macrophage function.

We have identified two potential mechanisms by which lactate drives macrophage responses:

a) GPCR signalling: The candidate will use Bioluminescent and fluorescence resonance energy transfer (BRET/FRET) and single molecule localisation microscopy (SMLM) to characterise lactate-elicited signalling cascades through GPR132/GPR81 in cell-line derived and primary macrophages.

b) Lipid droplet (LD) formation: LD-rich foamy macrophages are a hallmark of TB granulomas. Exposing lung macrophages to lactate results in a specific cytokine secretion profile, which is LD-dependent. The candidate will mechanistically elucidate the links between lactate-LDs and cytokine shifts. Mass spectrometry, CFUs/MGIT assays and in vitro experiments using inhibitors of LD formation will be employed.

2. Elucidating the mechanisms behind lactate's impact on mycobacterial fitness.

To study the impact of lactate on M.tb growth and fitness, we will take a two pronged-approach. We will test the effects lactate on cell envelope lipid content using a set of two-dimensional thin-layer chromatography (2D-TLC) systems designed to show the full profile of M.tb lipids including those involved in virulence. In parallel, we will conduct fitness and biochemical studies using a lldD2 null-mutant of M.tb. Changes in growth patterns (in vitro and in vivo), and a comparative lipid profile will be conducted using wild type, mutant and complemented strains, grown with or without lactate.

3. Assessing the therapeutic potential of targeting lactate sensing to treat TB disease.

To study local tissue responses, the candidate will use an ex vivo precision cut lung tissue slices (PCLTS) infection model which will be applied to human lung tissue (collaboration with Prof Thickett/Dr Scott). The model retains tissue architecture while maintaining native interactions between different pulmonary cell types. Lung slices will be challenged with the virulent M.tb H37Rv. CFU/MGIT assays, specific inhibitors of lactate pathways (ie. LD formation, GPCR signalling), ELISA/Luminex and immunofluorescence will be used to understand drivers of infection control.

This project represents a unique opportunity to ease the pathway towards novel treatments for an ancient disease, using cutting-edge science in an excellent, supportive research environment.

References

Llibre et al. Lactate cross-talk in host-pathogen interactions. Biochem J. 2021.

Stanley et al. Ongoing evolution of the Mycobacterium tuberculosis lactate dehydrogenase reveals the pleiotropic effects of bacterial adaption to host pressure. PLoS Pat.