Systems and synthetic biology: how the cell solves problems

Lectures: 1 session / week, 2 hours / session

The prerequisite for this course is Introductory Biology 7.012, 7.013, or 7.014. Also helpful would be at least one of the following courses:

18.03 Differential Equations

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.28 Molecular Biology

A millennial challenge in biology is to decipher how vast arrays of molecular interactions inside the cell work in concert to produce a cellular function. Systems biology, a new interdisciplinary field of science, brings together biologists and physicists to tackle this grand challenge through quantitative experiments and models. Molecular biology has provided us with a detailed understanding of the components that make up a cell – including the wealth of genes, RNAs, proteins and other macromolecules – as well as specific intracellular biochemical interactions. The diversity among species of specific cellular components in the context of broadly conserved chemical classes is one aspect of the beauty and elegance of biology. Systems biology is now revealing another elegant aspect of biology: when all these cellular components are integrated into a network of interactions, we find that there are common themes across a wide spectrum of organisms. There seems to be unifying principles that all organisms use to perform cellular functions.

In this course, we will discuss what these principles are. We will begin by considering several early papers in systems biology that identified key challenges faced by a cell in both single and multi-cellular organisms. One such challenge is that many intracellular processes, such as production of specific proteins and RNA molecules, are stochastic in nature. In other words, even within a population of cells that are genetically identical and live in the same environment, there can be significant variation from one cell to another in the level of individual gene products. This cell-to-cell variability can lead to stark phenotypic variation within a genetically and environmentally homogeneous population of cells. We will discuss how the network of genes in a cell is wired to control for the amount of noise and even take advantage of cell-to-cell variability for survival. Another challenge that a cell has to meet is reliably measuring how many key molecules are present in its surrounding environment so that it can respond appropriately. We will discuss papers that revealed that there is an ultimate limit to how accurately cells can "count" the number of extracellular molecules. We will then discuss how cells, from those in a bacterium to those in the embryo of a fruit fly, meet this challenge. Finally, we will discuss how researchers in the field of synthetic biology are using the new knowledge gained from studying naturally-occurring biological systems to create artificial gene networks capable of performing new functions.

The main objectives of this course are:

This course will focus on papers that have made significant conceptual contributions to systems biology. Two research papers will be discussed during each class session, and topics will include experimental methodology and the principles of experimental design, control experiments, and the interpretation of experimental data. This course will also introduce students to the theoretical aspects of biology. While some mathematical background will be helpful in this regard, it is not required.

This course is graded pass/fail. Grading will depend on student attendance, participation in class discussions and completion of two assignments.

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