Dr Raphael Dias Teixeira

Supervisor Details

Contact Details

r.diasteixeira@bham.ac.uk

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

My group works at the interface between structural biology and microbiology. We want to understand how bacteria survive, both when they are attacked by phages and when they stop growing and become tolerant to antibiotics. Much of our work follows nucleotides. NAD+ is destroyed by bacterial defence systems and exploited by phages, and its depletion pushes cells into dormancy through enzymes that cleave it. We are also interested in c-di-GMP, the signal that controls the switch between a motile lifestyle and life in a biofilm, and in how these signals are read by the proteins that bind them. We work mainly with Pseudomonas aeruginosa combining X-ray crystallography, cryo-EM and NMR with bacterial genetics, phage assays and live-cell imaging.

Supervision Style

In three words or phrases: Close support. Ideas welcome. Room to follow your own questions.

Provision of Training

The student will work directly alongside me at the bench, starting with microbiology and protein production before moving into structural work, so each method is learned at the right time. Learning will be supported by courses in structural biology and regular meetings to discuss the outcome of the experiments.

Progression Monitoring and Management

We will meet one to one every week to look at the data and agree what comes next, and the student will present to the group on a regular basis. At the start of each year we will write down what the project should achieve and revise it together when results send the work in a different direction.

Communication

My door is always open for questions. I sometimes send messages outside working hours because it suits my schedule, but I do not expect a reply on those times. I am open to talk about anything affecting your work, including things outside the lab.

Meetings

PhD Students can expect scheduled meetings with me at least once per fortnight. These meetings will be face-to-face and I am usually contactable for an instant response 3 or 4 days per week.

Work Patterns

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 5,000 words.

MIBTP Project Details

Primary supervisor for:

Nucleotide warfare between phages and bacteria, molecular mechanisms linking anti-phage defence to antibiotic tolerance

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).

Nucleotide warfare between phages and bacteria, molecular mechanisms linking anti-phage defence to antibiotic tolerance

Secondary Supervisor(s): Prof Andy Lovering

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Microbiology, Structural Biology)

Project Outline

Bacteria can survive antibiotic treatment in different ways. They can be resistant, or they can be tolerant, entering a dormant state in which antibiotics stop working even when no resistance gene is present. Tolerance is behind many chronic and recurrent infections, and it remains poorly understood at the molecular level. Phages, the viruses that infect and kill bacteria, are the most abundant biological entities on Earth and bacteria have evolved various defence systems to survive them. Recent work shows that these defences and dormancy work on the same cellular currency, the nucleotide pools. Defence systems degrade NAD+, ATP and dNTPs to starve an incoming phage, and the same depletion halts growth and leaves the cell tolerant to antibiotics. Phages in turn, have evolved counter-attack weapons that inhibit these systems or rebuild nucleotide pools.

This project asks how this works at the atomic level, and whether phage counter-defence strategies can be used to wake dormant bacteria and restore antibiotic killing. You will isolate phages on two pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii, under conditions in which dormancy is induced. Promising phages will be sequenced, and bioinformatic analysis will identify candidate genes for further characterisation. You will determine structures by X-ray crystallography and cryo-EM, characterise the proteins functionally, and use microbiology assays to test whether the strategies these phages use can resensitise bacteria to antibiotics.

You will be trained across structural biology, microbiology and bioinformatics in a group built around this interface. The project suits a student who wants hands-on protein work that stays connected to infection biology. The expected outcome is a mechanistic picture of how bacteria trade growth for survival, and a set of phage-derived strategies that can be tested against infections difficult to treat.

Co-supervisor on a project with Prof Andy Lovering.