Professor David Grainger PhD

• PhD (University of Birmingham)
• PGCE (University of Wolverhampton)
• BSc (University of Birmingham)

David’s first degree (Biochemistry) was awarded by the University of Birmingham in 1999. Following this, David trained as a teacher at the University of Wolverhampton (2000). Keen to reengage with the cutting edge research that he had been exposed to as an undergraduate, David returned to Birmingham to complete his PhD studies (2004). Employment as a post-doctoral research associate followed. During this time David developed the use of high-throughput techniques to map gene regulatory events in bacteria.

In 2008 David was awarded a prestigious Career Development Fellowship by the Wellcome Trust and used this grant to set up his research group at the University of Warwick. During this time David established collaborations with biophysical scientists and began studying DNA and its interactions at the single-molecule level.

In 2011 David relocated his research group to Birmingham. His current research is focused on deciphering the chromosome biology of pathogenic bacteria.

David teaches the bacterial cell cycle (Bio317), microbial genomics (BioM25 & BioM13) and research developments (BioM26). He is module lead on BioM25: "omics of pathogens".

David is always keen to welcome enthusiastic individuals to the lab. Contact him directly to discuss projects currently available. Details of funding available for PhD students in Birmingham are available on David's website.

Typically, the group takes students funded by the MIBTP doctoral training programme, or the Darwin Trust, at Birmingham. You will find that our projects are advertised on the webpages dedicated to these programmes and on findaphd.com

Professor Grainger's long-term interest has been to understand how genes are regulated. This impacts all aspects of bacterial cell behaviour and so allows us to work across multiple research themes and bacterial species. At present, work in our lab covers three general topics.

Understanding Multiple Antibiotic Resistance in Gram Negative Bacteria​​

Many bacteria are now resistant to some, or all, antibiotics. The multiple antibiotic resistance (mar) system, or its paralogs (e.g. ram and sox) in other species, play a key role in facilitating drug resistance. Consequently, mar has become a focus of our work. Briefly, the mar system encodes two transcription factors; a repressor called MarR and an activator called MarA. Usually, MarR prevents MarA expression. However, in multidrug resistant bacteria, the marR gene and intergenic region often contain mutations, which render MarR poorly active. Consequently, MarA is over-expressed. Once expressed, MarA switches on bacterial defence systems that protect cells against many antimicrobial compounds. Surprisingly, most genes targeted by MarA have not been defined. This is a significant omission; MarA targets will include hitherto undescribed determinants for antibiotic resistance and potential novel therapeutic targets. Our aim is to identify all genes controlled by MarA, or its paralogs, and define the underlying mechanisms of antibiotic resistance. They expect the resistance mechanisms to be broadly conserved in Gram-negative bacteria. 

They also have a growing interest in Acinetobacter baumannii; an organism that relies on chromosomal rearrangements to rapidly evolve new properties and adapt to its environment. These allow the bacterium to avoid killing by antimicrobial compounds, the human immune system, and more. They are currently trying to understand how DNA binding proteins control chromosomal rearrangements and so these important phenotypes.  

Bacterial pathogens

Many bacteria, including those that make the human body their home, are harmless. However, some bacteria interact with humans and other animals to cause disease. This often includes the production of toxic proteins that interact directly with host cells and alter their biology. The gene regulatory mechanisms used to control the production of such toxins, and other proteins important for the bacterium to colonise the host, are of great interest. They are currently trying to understand how pathogenic bacteria regulate genes to manage host colonisation and cause disease. Most of our work in this area is focussed on Vibrio cholerae, the causative agent of the pandemic disease cholera. They also have interests in enterotoxigenic E. coli (ETEC), Salmonella and Acinetobacter baumannii.

Controlling genes on a chromosome-wide scale​

The control of bacterial gene expression, particularly the control of transcription, has been studied since the dawn of molecular biology. Early studies established fundamental models of transcriptional control that still hold true today. However, recent work has revealed unprecedented complexity in transcriptional regulatory systems. These complexities are best understood using a combination of chromosome-wide and focused molecular techniques. A current research goal is to understand the intricate nature of transcription and its control at genes that have an unusual abundance of A and T nucleotides. Their work to date has shown that such genes have a tendency to fire undesirable transcriptional events that may impinge on aspects of biology as diverse as metabolism and evolution.

David is keen to engage with the public on scientific topics and was recently a runner up in the “science snaps” competition that utilised scientific imagery to arouse public interest in the sciences. David's laboratory run a Twitter feed where they discuss current issues in science. Take a look and find out what life is like in the Grainger lab!