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Chromatin and Transcriptional Memory

jake harrisHead of Group: Dr Jake Harris

We are interested in how chromatin impacts gene expression. Plants are a great model to study this question, as they rapidly adjust their transcriptional programs in response to fluctuations in temperature, light, rainfall and disease challenge. If plants are ‘primed’ by exposure to a particular stress once, they can respond much more effectively the next time. Thus, priming is akin to humans responding to a virus after immunisation against it. This memory of prior stress involves a re-sculpting of the chromatin landscape, so that certain genes can be reactivated or repressed more rapidly with subsequent challenge. The goal of our research is to discover how these mechanisms work, so that we can eventually control them to improve crop resistance and yield. This work could therefore provide key insight and tools to address the global challenges of sustainable food production in the face of climate change and population growth.

We employ the standard molecular biology toolkit, as well as cutting-edge genomic and bioinformatic approaches to assess chromatin dynamics, including ChIP-seq, RNA-seq and ATAC-seq. We are also harnessing the current revolution in precision genomics, by developing CRISPR based epigenome engineering tools. With these tools, we can deposit particular chromatin marks at precise genomic locations, and begin to ask fundamental questions concerning their effect on transcription. The ultimate goal is to use this knowledge to impart stress ‘memories’ into naive plants, so that they are primed and ready for challenges such as pathogen attack. 

The research in our lab is currently driven by two main questions:

What reads the histone code?

The eukaryotic genome is intimately physically associated with histone proteins, which are decorated with an array of post translational modifications. These histone modifications act as molecular ‘signposts’, providing the cell with information about whether the associated DNA should be turned ‘on’ or ‘off’. A staggering diversity of histone modifications have been described, and yet relatively little is known of how this combinatorial code is perceived and interpreted by the cell. Using proteomic and genomic approaches, we seek to identify, characterise and understand the function of histone mark readers.

What constitutes the primed chromatin state?

‘Priming’ refers to the phenomenon whereby plants respond more rapidly to a stress if they have been previously challenged, indicating that a memory of the initial trigger event has been maintained. Epigenetic marks on chromatin, which can be maintained between mitotic and sometimes meiotic divisions, can contribute this memory storage. Furthermore, some of these marks can increase the underlying gene’s responsiveness to future activation. However, many open questions remain, including: Are all stress response genes ‘prime-able’, or only some? What environmental and cellular conditions induce priming? What nuclear factors carry the priming signal? What distinguishes primed from non-primed chromatin, and how do these features impact transcription? By investigating these basic questions, we hope to build an understanding of the rules governing the chromatin basis of priming and transcriptional memory.

Dr Harris starts on 1st February 2021.

If you are interested in joining the lab, please get in touch by emailing: jake.harris88@gmail.com

The Department has carried out a comprehensive COVID-19 risk assessment process and has opened to allow research work to take place. To ensure the safety of our staff, a range of measures to reduce building occupancy and allow strict social distancing have been introduced, including increased cleaning and hygiene regimes. We are currently not accepting visitors so please continue to contact us by email until further notice.