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Department of Plant Sciences

 

jake harris
Head of Group: Dr Jake Harris
Royal Society University Research Fellow

We are interested in how chromatin impacts gene expression. Plants are exquisitely attuned to changes in environmental conditions, such as temperature, light, drought and disease challenge. Chromatin helps establish long-term, sometimes multi-generational, cellular memories of events that modulate the transcriptional response to a renewed attack.

This is akin to humans responding more effectively to a virus after natural or vaccine induced immunisation. In plants, such memories involve a re-sculpting of the chromatin landscape so that certain genes can be reactivated or repressed more rapidly with subsequent challenge.

Our recent research, along with collaborators, has led to the discovery of DNA methylation readers that activate and silence genes (Harris et al, Science 2018; Ichino et al, Science 2021) opening new avenues for exploring how cells encode and decode epigenetic states. The major 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 aims to provide key insight and tools to address the global challenges of sustainable food production in the face of climate change and population growth.

 

Our key questions are:

  • 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, altering 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.

  • How do genes and transposons co-exist?

Genomes are composed of functional elements (such as genes), and selfish elements that can self-replicate (such as transposons). Chromatin and epigenetic machinery play a key role in silencing transposons, while maintaining access to genes. How the cell discriminates between functional and selfish DNA remains an area of active research. This discrimination is especially challenging when things get crowded, ie when transposons and genes reside in close proximity. We are interested in unravelling the molecular mechanisms that perpetuate the memory of active gene states, thereby allowing genes, transposons, and silencing machinery to co-exist.

 

To address these questions, we employ a range of molecular biology approaches, as well as cutting-edge (epi)genomic, proteomic and bioinformatic techniques, to assess chromatin dynamics. 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 unravel fundamental questions concerning their effect on the chromatin landscape, memory and transcription.

 

Interested in joining the Lab?
The lab has opportunities for graduate students (PhD, Masters) and postdocs and I welcome inquiries. Prospective applicants should contact me directly (cjh92@cam.ac.uk). Prospective graduate students are encouraged to check out the University Postgraduate Admissions website for funding and deadlines. Postdoctoral applicants eligible for competitive fellowships (such as EMBO, HFSP and Marie Curie) are particularly encouraged. The University Postdoc Academy website has useful information.

 

Funding sources: The Royal Society, UK.

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