Research Areas

The Emili group’s research interests are diverse, but are generally centered on the exploration of the macromolecular networks in normal and diseased cells and tissues to reveal the fundamental mechanistic basis of biological systems.

 

Physical and functional interactions between gene products are essential to the formation and regulation of biological processes, while their disruption underlies pathology. Yet despite rapid advances in genomics, we still do not know which genes/proteins work together to support human health and development, or which interactions are altered in major diseases like cancer, neurodegeneration and heart disease.

To tackle these key questions, the Emili lab has assembled a productive, motivated and innovative research team to harness our world-class infrastructure and unique expertise in biochemistry, molecular biology, and systems biology to characterize molecular interaction networks with exceptional coverage, reliability, and mechanistic significance.

 

The Emili Group continuously develops and applies powerful proteomic, genomic and bioinformatic technologies, that leverage our world class infrastructure, and our innovative experimental pipelines to extend our team’s international leadership in interaction network biology. We publish ‘connectivity’ diagrams of exceptional impact useful to biomedical research groups worldwide, and we nurture and enhance our strong track record through mentorship and multidisciplinary training.

Notable publications by the Emili lab include:

 

 

  • Wan et al: “Panorama of ancient metazoan macromolecular complexes” Nature (2015) 525:339. We used our unique discovery platform to document >1 million protein interactions across virtually all multicellular species. Link to pubmed.

  • Havugimana et al: “A census of human soluble protein complexes” Cell (2012) 150:1068.  We used a unique integrative proteomics approach to identify hundreds of protein complexes in human cell lines, many linked to disease. Link to pubmed.

  • Babu et al: “Interaction landscape of membrane-protein complexes in Saccharomyces cerevisiae. Nature (2012) 489:585.  This is first ever global map of membrane protein complexes, which we reported for the yeast cell envelope. Link to pubmed.

  • Kislinger et al: “Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling.” Cell (2006) 125:173. We defined the tissue and subcellular localization patterns of thousands of mammalian proteins. Link to pubmed.

  • Krogan et al: ”Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature (2006) 440:637-43.  First article documenting the global physical interactome of macromolecules in a eukaryotic cell. Link to pubmed.

  • Butland et al:  “Interaction network containing conserved and essential protein complexes in Escherichia coli.”  Nature (2005) 433:531. The first global map of protein complexes for bacteria, defining a core network of conserved microbial assemblies. Link to pubmed.

Proteomics / Genomics / Systems Biology / Translation

 

 

The human genome encodes thousands of proteins which catalyze metabolites, relay signals, and form a dynamic cellular architecture. In healthy cells and tissues, these networks act in harmony, but this balance is usually disrupted in disease. Understanding and manipulating protein interaction networks is therefore a key goal for systems biology and precision medicine.

To address this challenge, the Emili laboratory uses world-class infrastructure, most notably high precision mass spectrometers, and our own innovative experimental and computational approaches, to generate ‘connectivity’ diagrams of unprecedented quality, scope and resolution that are broadly useful to biomedical research groups worldwide.  Because improper connectivity leading to aberrant protein function is a root cause of pathology, we also expect our interaction maps will improve understanding of the molecular basis of common diseases, such as heart failure and brain disorders.

Our multipronged approach is based on using protein tagging and an innovative biochemical co­fractionation strategy combined with quantitative mass spectrometry to characterize native macromolecules. Our unique platform affords an unprecedented opportunity to measure protein interactomes in primary cell types and tissues, such as neurons and brain, at different developmental stages and pathophysiological states.

Current interests include the systematic study of protein interaction networks underlying: (1) essential cell systems, biological processes and subcellular compartments of different cell types and tissues, which determine functional identify; (2) membrane-associated pathways that are important therapeutic drug targets; and (3) pathogens that cause drug-resistant human infections.  We have made substantive progress towards each of these objectives, and anticipate generating rich mechanistic insights from the thousands of unexpected associations we discover over the coming years. This work will spearhead many more high-impact papers and serve as lasting resources for the broader biomedical research community.

While our focus is on elucidating fundamental biological mechanisms, the Emili group is active in clinical translation. For example, with our network of clinical and industry (Roche Diagnostics) partners, we identified novel markers for early-stage heart disease (11 patents), including IGFBP7, an excellent marker of pre-symptomatic heart failure and prognostic marker in different cardiovascular disease patient populations that outperforms existing clinical assays.  With expert clinical and industry partners, we aim to translate the mechanistic knowledge we obtain from our network discoveries into new diagnostic and therapeutic leads. Our multipronged initiatives aim to document critical determinants of human health and development that are perturbed in common human pathologies like cancer, neurodegeneration and heart disease.

Precision Mass Spectrometry

 

 

Analytical excellence, technology development, and productive partnerships form the core ‘identity’ of the Emili group research. We continuously develop and apply multidisciplinary strategies to identify macromolecules of broad biomedical significance.

A major research focus of the Emili group is high precision, quantitative protein mass spectrometry. We have established state-of-the-art facilities for protein mass spectrometry, biochemical fractionation, primarily high performance chromatography, and high performance computational resources that allow us to map previously uncharacterized physical interaction networks. In particular, our newest generation ultra-high resolution/highest sensitivity/high speed mass spectrometers permit sample multiplexing, improved dynamic range and sequence coverage and high quantification accuracy, allowing for the characterization of even low abundance interaction partners.

Then, using innovative integrative computational and genetic/genomic approaches, we rigorously evaluate and independently validate the probabilistic networks we generate to deduce the major role(s) of novel protein complexes we discover with regards to functional relevance, developmental roles and disease relationships. With our expert biology and clinical partners, members of the Emili group perform in-depth follow-up mechanistic investigations to confirm the pathophysiological significance of the macromolecules we predict have strong but unexpected roles in development, disease and/or cellular processes.

By forging a ‘disruptive’ technology platform, the Emili team aims to nurture a transformative enterprise synonymous with research excellence, high impact and innovation for years to come.