Institute of Cellular Medicine

Staff Profile

Dr Daniel Rico Rodriguez

NU Research Fellow - Chromatin, Immunity and Bioinformatics

Background

Computational biology approaches to study epigenomic regulation in immune cells

I am University Research Fellow at the Institute of Cellular Medicine in the University of Newcastle, UK. I lead a computational biology group focused in studying the gene regulatory programs and epigenomes of immune cells. More specifically, we want to understand the molecular mechanisms underlying the differences of the immune system in men and women.

Before joining Newcastle University, I have been deeply involved in the bioinformatics coordination two large-scale projects: the Spanish ICGC-CLL Genome Project, studying the genome, epigenome and transcriptome of chronic lymphocytic leukemia (Kulis et al, 2012, Ferreira et al, 2014, Ecker et al, 2015), and the Blueprint Consortium  that has generated IHEC human reference epigenomes for most hematopoietic cell types and several leukemias (see IHEC papers). Moreover, I have led important methodological developments to dissect complex gene expression patterns from heterogeneous samples (Martinez-Garcia et al, 2014, Ecker et al, 2017), combining over hundred ChIP-seq experiments to reconstruct the first network of chromatin communication between proteins, histone marks and DNA modifications (Juan et al, 2016) and their relationship with the three-dimensional genome structure (Pancaldi et al, 2016). Finally, I have a long-standing interest in understanding how DNA replication and chromatin structure influence copy number variation and gene evolution (see our model in Juan, Rico et al, 2013).

An updated and complete list of publications is available in ORCID and Google Scholar. You can follow me on twitter or read our blog to stay tuned for information about my research.

Group members

Inmaculada Hernandez-Lopez, bioinformatician.

Kat Cheung, postdoctoral researcher.

Maninder Heer, PhD student.

Vacancies

There are not current open vacancies but we are always open to informal enquiries for PhD or Post-doctoral positions in this group.

Research

Sex-dependent gene regulation in immune cells

Despite the relevance of sexual dimorphism in both health and disease, there is still an important gap in our understanding of the role of sex in immune responses. The immune systems of men and women show remarkable differences, especially after puberty. For example, there is evidence showing significant differences in T-cell activation and proliferation, phagocytosis efficiency, cytokine production and response to vaccination. In general, reported differences include males being more exposed to infection risk than females, while in turn women show a higher risk of suffering autoimmune diseases but the biological mechanisms for these clinical-epidemiological observations remain unknown.

Any given cell’s developmental state and its future possible fates are believed to be determined by the epigenomic states of its chromatin. The epigenomic makeup of a cell not only conditions the genes that are switched on or off but also those (poised) genes that can be switched on under certain stimuli. In the context of autoimmunity, several studies have provided examples of epigenetic alterations that appear to be disease-associated and could offer a possible mechanism for the disproportionate sex ratios observed. However, most studies so far just focus on individual epigenetic features or particular genes and we need a more complete genome-wide picture of the molecular differences in immune cells in men and women.

A more complete genome-wide picture of the molecular differences in immune cells in men and women needs to be constructed to fully understand how the sex-encoded information of the genome influence their regulatory programmes. This genome-wide picture is challenging to construct because the high dimensionality of the epigenomic information, which it is dispersed in different un-connected databases and the need for new computational methods for analysis. Different data types must be processed, combined and interpreted.

We are developing integrative bioinformatics approaches to mine both publicly available data and new data generated by collaborators at Newcastle University. Focusing on the delineation of sex-dependent transcriptomic and epigenomic differences within the immune system, we are performing a systematic collection of the dispersed data and integrating the different layers in a common analytical framework. The ultimate goal of this effort is to connect the sex-specific gene expression programmes with the corresponding sex-specific chromatin configuration.

Funding

Wellcome Trust Seed Award in Science - ‘Sex-dependent gene regulation in immune cells’  

Teaching

I regularly offer computational biology research projects for Msc and MRes students at the Faculty of Medical Sciences.

I am currently co-supervising an Systems Biology MRes project entitled 'Chromatin modifications during mitosis: a network approach based on ChIP-seq data' in collaboration with Jonathan Higgings.

Publications