About us

We are a new research group opening in October 2021 at Single Molecule Science: the EMBL Australia node of the University of New South Wales. We are currently recruiting PhD students and postdocs. Please contact Scott if you are interested in joining or collaborating.

UNSW

People

Scott Berry

Scott Berry

Group leader

Hi! I am Scott. After completing my undergraduate studies in Theoretical Physics and Biology at the University of Adelaide and the University of Western Australia, I moved to the UK for my PhD at the John Innes Centre. There, I worked with Caroline Dean and Martin Howard, combining theoretical and experimental biology approaches to understand mechanisms of epigenetic memory in Arabidopsis thaliana. I then moved to Switzerland as a HFSP postodctoral fellow, working with Lucas Pelkmans at the University of Zurich. In Lucas' group, I shifted model systems from plants to mammalian cells, and became immersed in the wonderful world of modern single-cell biology – focusing on understanding the mechanisms by which cells coordinate gene expression with cell size. From October 2021, I will be a group leader at Single Molecule Science at the University of New South Wales.

Research

We are interested in the mechanisms used by cells to regulate gene-specific and global RNA abundance – ranging from epigenetic memory and cellular decision-making to global RNA metabolism in the context of cellular physiology. We seek to generate a quantitative understanding of these processes.

Our research methodology is a combination of ‘top-down’ (data-driven) and ‘bottom-up’ (hypothesis-driven) approaches. We make extensive use of high-throughput microscopy and automated image analysis, which enables detailed measurement of quantitative cellular phenotypes (for example, the abundance and localisations of specific proteins or RNAs) across large cell populations. Resulting datasets are then analysed using a variety of methods from data science. We complement these image-based approaches with functional genomics experiments, based on next-generation sequencing – providing exquisite genomic resolution, and use perturbation experiments including genome and epigenome-editing to test specific hypotheses.

Effects on gene expression of CRISPR-KO using smFISH

Projects in the lab are often underpinned by construction of minimal mathematical models at the molecular level, which we use as a tool for exploring possible explanations of experimental results and prioritising future experiments.

We believe that the best science happens in the overlap between fields. We strive to build a diverse team and foster collaborations across fields and disciplines.

Stability and plasticity of epigenetic memory

The chromatin of individual genetic loci can be set into molecular ‘states’ that control the expression of the underlying genes, and in some cases even instruct their own inheritance – acting as local epigenetic memory elements. When necessary, however, chromatin can also be reliably switched from one state to another – by processes that involve coordinated changes to the histone modifications, accessibility of regulatory sequences, and expression states of the underlying genes.

We are interested in the interplay between gene-specific diffusible regulatory factors (e.g. transcription factors), which tend to have continuous (analogue) control over gene expression, and heritable chromatin states (e.g. Polycomb-repressed chromatin), which tend to promote bi-modal (digital) stable expression states. To study these processes we use in vitro differentiation of epithelial cells from human induced pluripotent stem cells.

Further reading:
Yang, Berry et al., Science, 2017
Berry et al., Cell Systems, 2017

Integrating local and diffusible signals at chromatin Mechanistic model of self-perpetuating active and repressed chromatin states.

Global control of RNA metabolism

Mammalian cells coordinate RNA production rates with cell size to ensure RNA concentration homeostasis. We discovered that this process relies on adapting transcription rates according to nuclear mRNA concentration, so that overabundance of nuclear mRNA leads to transcriptional repression. This mechanism involves mRNA-based regulation of the activity of RNA Polymerase II, which in turn determines polymerase abundance. We are interested in further dissecting the interplay between the transcriptional machinery, nuclear RNA export and RNA degradation factors that act in concert to ensure robust mRNA concentration homeostasis.

Further reading:
Berry et al., bioRxiv, 2021

Feedback from RNA production

High-dimensional cellular phenotyping

4i In recent years, technological advances have made it possible to visualise tens to hundreds of proteins in single cells. This has brought with it the ability to accurately quantify the high-dimensional relationships between protein abundances and their modification states, as well as the cell-to-cell variability of their subcellular localisation and co-localisation.

We use Iterative Indirect Immunofluorescence Imaging (4i) throughout our research to comprehensively evaluate changes to cellular phenotypes in the context of cellular differentiation and upon perturbation of RNA metabolism. These datasets are extraordinarily rich in information, however much of this information is not easy to interpret using existing approaches. In collaboration with Lucas Pelkmans' and Fabian Theis' research groups, we are also currently developing new computational image analysis workflows to facilitate analysis of these data at the subcellular, cellular and population scales.

Further reading:
Gut et al., Science, 2019

Multiplexed Cell Units

Applying pixel-clustering approaches to highly-multiplexed 4i image data identifies subcellular structures in an unbiased manner. In this case, we focused on the nucleus: revealing organelles such as nuclear speckles, Cajal bodies, PML bodies and the nucleolus.

Publications


Preprints

Nuclear RNA concentration coordinates RNA production with cell size in human cells

Berry, S.^, Müller, M. and Pelkmans, L.^
bioRxiv | PDF | bioRxiv
^ Corresponding authors


2021

High content genome-wide siRNA screen to investigate the coordination of cell size and RNA production

Müller, M., Pelkmans, L., and Berry, S.
Scientific Data | PDF | Journal | Data


2017

Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression

Berry, S., Rosa, S., Howard, M., Bühler, M., and Dean, C.
Genes & Development | PDF | Journal

Slow Chromatin Dynamics Allow Polycomb Target Genes to Filter Fluctuations in Transcription Factor Activity

Berry, S., Dean, C., and Howard, M.
Cell Systems | PDF | Supplementary | Journal | Commentary

Distinct phases of Polycomb silencing to hold epigenetic memory of cold in Arabidopsis

Yang, H.*, Berry, S.*, Olsson, T.S.G., Hartley, M., Howard, M., and Dean, C.
Science | PDF (accepted version) | Journal
* Equal contribution


2015

Local chromatin environment of a Polycomb target gene instructs its own epigenetic inheritance

Berry, S., Hartley, M., Olsson, T.S.G., Dean, C., and Howard, M.
eLife | PDF | Journal

Environmental perception and epigenetic memory: mechanistic insight through FLC

Berry, S., and Dean, C.
The Plant Journal | PDF | Journal


2014

Lipopolysaccharide O antigen size distribution is determined by a chain extension complex of variable stoichiometry in Escherichia coli O9a

King, J.D.*, Berry, S.*, Clarke, B.R., Morris, R.J., and Whitfield, C.
Proceedings of the National Academy of Sciences | PDF | Supplementary | Journal
* Equal contribution


2012

Illustrations of Mathematical Modeling in Biology: Epigenetics, Meiosis, and an Outlook

Richards, D.*, Berry, S.*, and Howard, M.
Cold Spring Harbor Symposia on Quantitative Biology | PDF | Journal
* Equal contribution


2011

qwViz: Visualisation of quantum walks on graphs

Berry, S.D., Bourke, P., and Wang, J.B.
Computer Physics Communications | Journal

Two-particle quantum walks: Entanglement and graph isomorphism testing

Berry, S.D., and Wang, J.B.
Physical Review A | Journal


2010

Quantum-walk-based search and centrality

Berry, S.D., and Wang, J.B.
Physical Review A | arXiv | Journal