Systems Biology

A Personal View


Sitabhra Sinha

The course is called Systems Biology: A Personal View rather than simply Systems Biology because, being a relatively new field, one course on the subject can look radically different from another in terms of content as well as treatment - and the exact structure of the course depends pretty much on who is teaching it.

The common minimum on which most people agree is that systems biology essentially seeks to figure out how to bring together knowledge about the component parts in order to understand the whole (the system). For example, if we want to understand how the cell responds appropriately (most of the time) to a wide variety of signals in an extremely noisy environment, we need to pull together our knowledge of a large number of signaling pathways which involve a wide variety of molecules. There are several systems biology courses which only deal with this aspect - and from this point of view, systems biology is all about constructing a large-scale detailed computational model that will explain how a cell functions. As such, this approach has been criticized by several scientists - including the Physiology Nobel Laureate Sydney Brenner (see his 2009 lecture at the Salk Institute).

However, other systems biologists feel that just focusing on questions at the level of the cell, is missing the whole point. For example, on generalizing the above problem, we realize that essentially the same problem is confronted by the multi-cellular organism where the nervous system somehow solves this problem. Are similar principles being used both at the level of the cell and at the level of the organism - and if so, what are these "universal" principles ? That is a systems-level question, which is different from the questions that will be asked by cell biologists or neuroscientists who are more interested in the exact "wetware" by which the problem is solved in the specific system they are interested in.

One can easily see that a host of questions one can ask at one level of biological organization (e.g., the cell) have analogs at other levels (e.g., the organism, the population or the food web). These could be questions about communication efficiency, computational capability, dynamical stability, robustness to environmental noise, etc. of the corresponding systems. Often it is more useful to generalize the problem from the specific biological setting and frame it in terms of useful theoretical constructs such as networks, at other times we may be interested in a general phenomenon such as wave propagation. I have therefore organized the course around several such "tools for thinking" about biological problems (to paraphrase the title of Conrad Hal Waddington's book Tools for Thought, a must-read for any theoretical/computational biologist) - viz.,
(i) Networks,
(ii) Oscillations (temporal patterns),
(iii) Shapes (spatial patterns) and
(iv) Waves (spatio-temporal patterns)
[Note that, networks are also "spatial" patterns - although, in general, the pattern is in a non-physical abstract space]

In the 30-odd lectures of this course, we will first introduce each "tool" and then apply it to various biological phenomena. On the way, we will look at how this perspective can help us look at certain diseases - such as cancer, epilepsy and cardiac arrhythmias - in a new light.
 

Class Schedule: Tuesday and Thursday (11:30-1:00)
 

8/1/15: Introduction

13/1/15: Antecedents and Course Outline

20/1/15: Networks: Basic Concepts

22/1/15: Networks: Basic Concepts II

27/1/15: Guest Lecture: Areejit Samal (IMSc)

3/2/15: Networks: Models I

5/2/15: Networks: Models II

10/2/15: Proteins as Networks

12/2/15: Proteins as Networks: Centrality and Core-Periphery

17/2/15: Intra-cellular Systems I: Regulatory Networks and Motifs

19/2/15: Intra-cellular Systems II: Protein-Protein Interaction

24/2/15: Intra-cellular Systems III: Metabolism and Modularity

26/2/15: Importance of Modularity in Networks

3/3/15: Intra-cellular Systems IV: Signal-transduction and networks

5/3/15: Modularity and Inter-cellular networks

10/3/15: Guest lecture: MicroRNAs as modulators of signaling pathways in cancer cells by Devarajan Karunagaran (IIT Madras)

13/3/15: Mid-term examination

17/3/15: Network Medicine

19/3/15: Interactions in Ecology

24/3/15: Food Webs & Stability of Ecological Networks

26/3/15: Network Epidemiology

31/3/15: Temporal patterns and biological oscillators

2/4/15: Biological oscillators: Hopf Bifurcation & Glycolysis

6/4/15: Temporal patterns: Discrete time models in biology

7/4/15: Building elements for biological circuits

8/4/15: Spatial Patterns in Biology: Turing mechanism

9/4/15: Turing patterns in biological systems

15/4/15: Guest Lecture: Areejit Samal (IMSc)

16/4/15: Guest Lecture: Areejit Samal (IMSc)

21/4/15: Waves in Biology: Excitable Media

23/4/15: Waves in Biology: From cells & tissue to populations

27/4/15: Waves in Biology: Cardiac Arrhythmia

28/4/15: Waves in disordered excitable media: Obstacles, Gradients, & Pinning

29/4/15: Synchronization in Biology

30/4/2015: Oscillations, Waves and Synchronization in Uterine Tissue

12/5/2015: End-sem presentations
 
 

Assignments

Assignment 1 (due January 16, 2015)

Assignment 2 (due February 19, 2015)

Textbooks:
There is, unfortunately, no book that covers the course in its entirety and I only mention a few below that I will use for several lectures. For networks, we will consult
Mark Newman, Networks: An Introduction,
possibly the best textbook on the subject. For network motifs, we will look at
Uri Alon, An Introduction to Systems Biology.
For patterns, a very good non-technical book is
Philip Ball, The Self-Made Tapestry.
However, for the course we will use more technical books - initially
Steven H Strogatz, Nonlinear Dynamics and Chaos
and later
Lee Segel, Modeling Dynamic Phenomena in Molecular and Cellular Biology.
For waves, we will use
Jose Jalife et al, Basic Cardiac Electrophysiology for the Clinician
(don't be fooled by the title - it is much more general than just cardiac electrophysiology and certainly will appeal to a much broader audience than just clinicians), as well as, material from our recent book
Sitabhra Sinha and S Sridhar, Patterns in Excitable Media: Genesis, Dynamics and Control.

Web resources for Systems Biology:
Uri Alon's Systems Biology course, 2014