The virtual liver: a multidisciplinary, multilevel challenge for systems biology

Hermann-Georg Holzhütter1, Dirk Drasdo, Tobias Preusser

  • 1Institute of Biochemistry, University Medicine Berlin (Charité), Berlin, Germany.

Insights

Researchers are developing a comprehensive computational model of the human liver. This systems biology approach aims to simulate liver functions for both healthy and diseased states, aiding drug development and understanding liver diseases.

Area of Science:

  • Systems biology and systems medicine
  • Computational modeling of human organs

Background:

  • The liver is a critical metabolic organ involved in detoxification, homeostasis, and acute phase response.
  • Liver toxicity is a major cause of drug development failure, and liver disorders are linked to prevalent diseases like diabetes and fatty liver disease.
  • Current understanding of complex liver physiology necessitates advanced modeling approaches.

Purpose of the Study:

  • To present the concepts and approaches for developing a whole-organ model of the human liver.
  • To represent central liver physiological functions under normal and pathological conditions using computational methods.
  • To integrate processes across hierarchical levels in space, time, and structural organization within the liver model.

Main Methods:

  • Development of a multidisciplinary research program focused on whole-organ liver modeling.
  • Construction of a large battery of interconnected submodels representing liver anatomy and physiology.
  • Integration of multi-scale processes to capture complex liver functions.

Main Results:

  • Outlined the general architecture for the ambitious whole-organ liver model.
  • Presented the initial steps taken towards achieving the goal of a comprehensive liver simulation.
  • Established a framework for integrating diverse biological data into a unified model.

Conclusions:

  • The development of a whole-organ liver model is a significant advancement in systems medicine.
  • This model holds promise for understanding liver diseases and improving drug safety and efficacy.
  • The presented approach provides a foundation for future research in computational liver physiology.

Related Concept Videos

Hepatic Portal System01:21

Hepatic Portal System

The hepatic portal system, a critical part of our circulatory framework, transports nutrient-laden, deoxygenated blood from the gastrointestinal tract and spleen to the liver. This ingenious system plays an indispensable role in maintaining our body's metabolic equilibrium.
At its core, the hepatic portal vein is the result of a confluence of the superior and inferior mesenteric veins along with the splenic vein. Each of these veins has a unique role. The superior mesenteric vein is responsible...
Liver Physiology01:30

Liver Physiology

The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of  70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can also...
Gross Anatomy of the Liver01:17

Gross Anatomy of the Liver

The liver, the largest gland within the human body, is a firm and reddish-brown organ. This wedge-shaped structure weighs approximately 1.5 kg and occupies a significant portion of the right hypochondriac and epigastric regions. It extends more to the right of the body's midline than to the left.
Located under the diaphragm, the liver is almost entirely ensconced within the rib cage, providing it with substantial protection. Except for the superior most bare area, the liver's surface is covered...
Synthetic Biology02:55

Synthetic Biology

Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
Golden rice
Golden rice is a genetically modified...
Overview of the Vascular System01:20

Overview of the Vascular System

The vascular system comprises an extensive network of arteries, capillaries, and veins. The vascular system can be broadly divided into the blood and lymphatic systems. Typically, blood vessels can be categorized into three histological regions: tunica intima, tunica media, and tunica adventitia. The tunica intima consists of a single layer of endothelial cells attached to the basal lamina. Underlying the basal lamina is a connective tissue layer and an elastic lamina that gives stability and...
Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model01:14

Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model

The link model is a fundamental pharmacokinetic-pharmacodynamic (PK–PD) approach to account for delayed drug responses when the observed effect does not immediately correlate with the drug's plasma concentration peak. This delay is mathematically addressed by introducing an effect compartment concentration, Ce, which is kinetically linked to the plasma concentration, Cp, via a first-order rate constant, ke0. The linkage allows for a more accurate prediction of drug effects over time. A higher...