Our Research Interests
Our research sits at the intersection of gene regulation, human evolution and population genetics. We are particularly interested in the role gene regulatory processes have played throughout human evolution and continue to play in giving rise to present-day human diversity, and the implications this has for the widespread adoption of personalised medicine. Because gene regulation is not easily predicted (at least for now!) from sequence-level data, we use multiple a combination of computational biology and functional genomics approaches to understand the means by which cellular mechanisms interact to regulate gene expression, and, under the action of natural selection, ultimately give rise to inter-species or population-level differences. Our work directly speaks to, and seeks to remedy, the lack of diversity and representation in human genomics today.
Currently, one of our main focuses is understanding the challenges of peopling Southeast Asia, with a particular interest on the Indonesian archipelago and the interactions between Homo sapiens and other, now extinct, regional hominins, such as the Denisovans.
Ongoing research in the group makes use of multiple cutting-edge approaches, including induced pluripotent stem cells (iPSCs), massively parallel reporter assays (MPRAs), functional genomics assays at bulk and single cell resolutions and machine learning, bringing together multiple disciplines to address questions that cannot be tackled independently by any single one of them. We are also one of the few groups worldwide with an established record in generating iPSC lines from non-model organisms such as great apes.
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The Denisovans were archaic hominins who made substantial contributions to the genomes of the present-day peoples of Papua New Guinea and, more broadly, Southeast Asians, but the biological consequences of this are poorly understood. We combine multiple computational and experimental approaches (functional genomics, machine learning, MPRAs) to understand what their DNA means today to the people who carry it.
We have been working with researchers in Indonesia to quantifying functional genetic diversity across the Indonesian archipelago (the world’s fourth largest country by population!) at the bulk and single-cell levels. We want to understand the interplay of genetic and environmental forces in shaping gene expression and, more broadly, human phenotypes, in this part of the world, and how these compare to other populations worldwide.
Multiplexed assays of variant effects (MAVEs) are a set of methods that allow the experimental dissection of many genetic variants simultaneously. We are particularly interested in exploring the potential of massively parallel reporter assays, which test the regulatory potential of thousands of genetic variants at once, as tools in evolutionary biology.
The lack of diversity in human genetics datasets has been well-documented, especially at the DNA level. We are interested in looking beyond that, and quantifying both the downstream consequences of existing biases in the field, as well as diversity in other modalities of data, with a current focus on transcriptomics.