Dr Hasan Yesilkaya

Supervisor Details

Contact Details

Respiratory Sciences, University of Leicester

Scientific Background

Research Interests

Microbes encounter fluctuating nutrient and physical environments in host tissues. In this dynamic milieu bacteria should be able to obtain the host nutrients and metabolise them for efficient replication and virulence. However our knowledge of how microbes maintain their survival in vivo is very limited. I have been studying microbial physiology and metabolic adaptation using Streptococcus pneumoniae as a model organism to understand microbial in host survival and virulence. My ultimate research goals are to define critical metabolic microbial networks associated with virulence in different host niches and target these pathways pharmaceutically. The particular topics I study include: mechanisms by which microbes cleave and metabolise host-derived nutrients the impact of genetic and environmental factors on microbial colonisation and virulence the role of quorum sensing systems on pneumococcal physiology and in host survival.

Scientific Inspiration

I am inspired by the pioneers of microbiology, such as Robert Koch, Ignaz Semmelweis, and Louis Pasteur. These scientists have done highly sophisticated work with the power of their vision in an era when sophisticated research technology was not available to them.

Supervision Style

In three words or phrases: goal-driven, student-centred, collaborative.

Provision of Training

Initially, you will be supported in some of the key techniques. As your project progresses you are expected to establish techniques independently.

Progression Monitoring and Management

I like to be kept up to date, and will expect to see evidence of method development/data generation results on a weekly basis.

Communication

You can communicate with me via e-mail or if it is urgent by phone. I would like to have one to one meetings as well as group meetings where we can communicate.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once a week

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 fortnight

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

Working Pattern

Work in my lab requires being present on site (be it in a laboratory or at a field site) during core hours (or a subset if working part 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:

How does stress make us sick?

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).

How does stress make us sick?

Secondary Supervisor(s): Professor David Cousins

University of Registration: University of Leicester

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

Project Outline

Stress is a potent driver of various diseases. There is strong evidence that stress decreases the effectiveness of the immune response. Much less well understood is whether and how stress directly modulates pathogens via alterations in their gene expression, phenotype, and pathogenic potential. Multiple studies suggest links between stress hormones and bacterial pathways in Gram-negative pathogens. Specifically, catecholamines (CA) released by the host can modulate the expression of virulence determinants and promote iron uptake. Further, a limited number of recent studies suggest that CAs also modulate the physiology of Gram-positive pathogens by promoting biofilms, growth or iron uptake. However, the methods by which Gram-positive bacteria detect and react to CAs signals are still unknown. The objective of this proposal is to gain basic understanding of the regulatory mechanisms, both in vitro and in vivo, that underpin the bacterial response to stress and how host cues affect them. We want to gain insights into how important human pathogen Streptococcus pneumoniae (Spn) responds to stress using in vitro, ex-vivo, and in vivo models of disease. The study builds on our recent work where we demonstrate that Spn senses CAs via a two-component system and responds by changes in growth, biofilm development and iron uptake. Moreover, we find that Spn exposure to a CA (neuroepinephrine norepinephrine (NE)) increases bacterial titres in the lung, while maintaining comparable titres in the upper respiratory tract (URT). Spn colonizes the nasopharynx as a commensal, yet it can also disseminate from the URT to the lungs, middle ear, blood, heart or brain causing mild to severe disease. We hypothesize that stress promotes the transition of Spn from a commensal to a pathogen and propose three aims to address the interaction of stress and Spn biology.

Aims

Aim 1: Characterize the molecular circuit(s) that confers responsiveness to NE and its phenotypic consequences using mutant analysis and gene expression studies.

Aim 2: Establish whether and how NE-sensing influences biofilm development and adhesion to host cells.

Aim 3: Evaluate the impact of stress hormones in a murine model of Spn infection and stress. We will use in vivo and ex-vivo studies to uncover how stress-exposed immune cells interact with Spn.

Our results could inform the development of strategies that act by disrupting damaging aspects of the hormonal-to-bacteria information exchange, and in so doing, provide new areas for prevention or treatment of Spn infections, for example by reducing stress induced infection susceptibility.

Techniques

Techniques that will be undertaken during the project:

Microscopy.
Microbiology techniques.
RNAseq.
Flow cytometry.
Phagocytosis assay.
Array tomography.
Animal models of infectious disease.

References

Alghofaili F, Najmuldeen H, Kareem BO, Shlla B, Fernandes VE, Danielsen M, Ketley JM, Freestone P, Yesilkaya H. Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs. mBio. 2021 Dec 21;12(6):e0256921. doi: 10.1128/mBio.02569-21. Epub 2021 Oct 26. PMID: 34696596; PMCID: PMC8546540.