A guide for prospective Principal Investigators
The Cori Institute is being built to make metabolism quantitative, predictive and engineerable.
In its formative phase, Cori is deliberately casting a wide scientific net to attract exceptional investigators from across biomedicine, computation, engineering and adjacent disciplines. The 30 areas below define the institute’s opportunity space: they are not 30 separate programmes, nor a checklist for applicants.
What we are looking for. Original research programmes that can deepen, connect or reshape this opportunity space. We especially value ideas that create productive bridges between biological discovery, quantitative modelling and intervention.
The Cori Engine
The Cori Engine is a closed, iterative system in which metabolism, mathematical modelling and metabolic engineering continuously inform one another. Biological processes are not only observed: they are quantitatively described, predicted, perturbed and ultimately shaped.
Data from cellular systems, organoids, reconstituted pathways, clinical cohorts and exposomic measurements feed models across scales. Those models generate hypotheses and design principles that guide targeted interventions. Engineering - through chemistry, protein design, pathway rewiring, cellular systems and devices - then perturbs or reconstructs metabolic states, producing new data and revealing system constraints.
In short: Data -> Models -> Intervention -> New data and constraints.
From the molecular architecture and logic of human metabolism to the ecometabolome
Cori’s scientific focus spans molecular, cellular, organismal and environmental metabolism. A central ambition is a comprehensive quantitative model of human metabolism - a “digital metabolic twin” - capable of predicting physiological states, disease trajectories and therapeutic responses. The institute will address major human disorders including cardiovascular disease, diabetes, neurodegeneration, cancer, ageing and fertility, while also extending to environmental interfaces such as nutrition, pollutants, xenobiotics and other chemical exposures.
The institute is explicitly intervention-oriented: it aims not only to understand metabolic systems, but to design drugs, proteins, pathways, biological circuits and biotechnological solutions. Strong interfaces with the biopharmaceutical, food, environmental and technology sectors will help convert scientific insight into applications.
Spanning across scales, an important central , a seed, is the spatial architecture of metabolism: the physical organisation of metabolic logic. Metabolic efficiency depends not only on enzymes and pathways, but also on the three-dimensional organisation of enzymes, transporters, organelles and transient molecular assemblies that coordinate metabolic flow. Cryo-electron microscopy, cryo-electron tomography and complementary imaging will connect structure across molecular, organellar and cellular scales to predictive modelling, drug discovery and metabolic engineering.
Broad at the start, strategic over time. Early recruitment is intentionally opportunistic and open. As investigators start their activity at the Cori, synergistic efforts and emerging interests will assemble into areas of critical mass around Cori’s flagship programmes. Exceptional proposals outside an obvious flagship remain fully within scope if they advance the institute’s core mission.
5 Emerging flagship programmes
The flagships indicate strategic directions in which Cori expects to build shared capabilities and critical mass. They are designed to connect investigators rather than restrict the scientific scope of recruitment.
1. Quantitative Human Metabolism Model. Build a predictive, extensible model of human metabolism across scales - ultimately enabling a digital metabolic twin for defined physiological and pathological perturbations.
2. Brain Metabolism, Neurodegeneration and Ageing. Understand how metabolic state, bioenergetics and cellular interactions shape brain function, degeneration and ageing, and identify actionable points of intervention.
3. Metabolic Drug Targets. Discover and validate metabolic vulnerabilities and intervention points, with particular strength in mitochondria, membranes, transporters and chemical biology.
4. Exposome and Human Metabolism. Define how nutrition, environmental chemicals, lifestyle and cumulative exposures reshape human metabolic and endocrine states across populations and individuals.
5. Metabolic Engineering and Intervention. Design and rewire metabolic systems using protein and enzyme engineering, synthetic pathways, cellular programmes, microbial communities, chemical modulators and devices.
30 areas of scientific opportunity
These areas map the initial boundaries of Cori’s interest. Candidates may sit squarely within one area, bridge several, or define a new intersection between them. Scientific excellence and the potential to contribute to Cori’s broader ecosystem matter more than exact categorical fit.
I. Modelling, Prediction, and Theory
1. Comprehensive quantitative model of human metabolism
2. AI-driven and genome-scale metabolic modelling
3. Dynamic metabolic flux, real-time sensing, and nonlinear systems modelling
4. Evolutionary constraints and design principles of metabolic networks
II. Molecular Mechanisms and Regulatory Logic
5. Mitochondrial energy homeostasis, life cycle, and bioenergetics
6. Post-translational and signalling control of metabolism
7. Metabolic control of cell identity, state transitions, and biomolecular condensates
8. Temporal organisation of metabolism
III. Spatial, Structural, and Compartmental Metabolism
9. Structural metabolism and 3D cell anatomy
10. Spatial, single-cell, and compartmental metabolism
11. Transportome, chemical exchange, and inter-organ metabolic communication
IV. Perturbation, Engineering, and Design
12. High-throughput enzymology and droplet microfluidics
13. Protein-binder perturbation and functional interference technologies
14. Discovery and design of small-molecule and peptidic metabolism modulators
15. Metabolic engineering and design of new pathways
16. Synthetic and evolutionary metabolism
V. Human, Disease, and Trans-Organismal Metabolism
17. Clinical metabolism, patient data, and translational metabolic medicine
18. Muscle metabolism, the Cori cycle, and systemic energy balance
19. Bioenergetics, ageing, and neurodegeneration
20. Fertility, hormone metabolism, and endocrine disruption
21. Immunometabolism, infection, and nutritional defence mechanisms
22. Microbiome-metabolome interface and trans-organismal metabolism
VI. Environment, Exposome, and Society
23. Exposome, foodome, pollutants, and human metabolism
24. Metabolic transformation and clearance of environmental chemicals
25. Citizen-powered real-time exposome and metabolism mapping
26. Paleo-metabolism and historical metabolic states
VII. Philosophy, Law, and Socio-Economic Sciences
27. Ethics and philosophy of metabolism research
28. Law, governance, regulation, and psychology of clinical and environmental metabolism and exposome research
29. Economics of innovation and research ecosystem building
30. History of environmental-health relations
Cori Pairs. Areas 27-30 are envisioned in the context of metabolism research at Cori and, initially, primarily through the Cori Pairs programme in combination with a scientist from the biological, medical, computational or engineering domains.