Ayush Pandey

ENGR 164: Introduction to Biological System Design.

Course Logistics

Instructor: Ayush Pandey (e-mail: aypandey@hmc.edu)
Lectures: Tuesday and Thursday, 2.45 pm - 4 pm, location: on Zoom until 31st Jan. Then, at Shanahan 2407.
Office hours: Monday 12 - 1pm on Zoom and Tuesday 4-5 pm after class. Schedule any other office hour as you may need by sending me an email.
Piazza: For all class related discussion, homework Q&A, and general announcements.
GradeScope: For assignment submissions and tracking grades for the problem sets.

This is the course homepage for ENGR 164, listed as Introduction to Biomedical Engineering in the Engineering course catalog at Harvey Mudd College for Spring 2021-22 semester. The actual course title is Introduction to Biological System Design. This course is intended for juniors and seniors interested in the computationally exploring the design of natural and engineered biological systems. After completion of the course, students will be able to:

understand the basics of biological systems design
develop mathematical models for biological circuits
use numerical approaches to understand and analyze biological data

Course Description

E164. Introduction to Biological System Design. Spring Semester at Harvey Mudd College.
Credits: 3 (2.5 hr lecture, 0 hr lab, 6 hr homework).
Prerequisites: CS5 and E79 or by instructor's permission.
Course Topics: Introduction to the broad fields of systems and synthetic biology by describing the basic biological processes, mechanisms, and components of biological designs. Particular topics include: gene regulatory networks, transcriptional and translational regulation, common motifs in biological circuit designs, chemical reaction network modeling for biological systems, mathematical analyses using differential equations, calculus, and algebra for biological models, and two case studies of biological systems. The course will be taught in Python language — so we will use programming in Python to numerically or analytically understand the topics.

Lecture Schedule

Date	Topic	Homework	Reading
Week 1 18 Jan 20 Jan	Introduction: Course logistics Overview: Biological Systems Design Introduction to Python Introduction to Systems and Synthetic Biology	HW #1 (PDF) HW #1 (IPYNB) Out: 18 Jan Due: 25 Jan HW #1 Solution PDF (HMC only) HW #1 Solution IPYNB (HMC only)	week1_python_intro.ipynb week1_python_intro.pdf Review: Computational Biology
Week 2 25 Jan 27 Jan	Biological Experiments and Data Cell Growth Dynamics	HW #2 (PDF) HW #2 (IPYNB) Out: 25 Jan Due: 2 Feb HW #2 Solution PDF (HMC only) HW #2 Solution IPYNB (HMC only)	week2_data_analysis.ipynb week2_data_analysis.pdf BFS Section 1.2 Review: Synthetic Biology
Week 3 1 Feb 3 Feb	Core Biological Processes - I Transcription and Translation Modeling Biological Processes	HW #3 (PDF) HW #3 (IPYNB) Out: 1 Feb Due: 8 Feb HW #3 Solution PDF (HMC only) HW #3 Solution IPYNB (HMC only)	week3_intro_ode.ipynb week3_intro_ode.pdf BFS Section 2.2 PBoC Section 3.2.1: Timing the machines of the central dogma
Week 4 8 Feb 10 Feb	Core Biological Processes - II Gene Regulation Phenomenological Modeling of Biological Systems	HW #4 (PDF) HW #4 (IPYNB) Out: 8 Feb Due: 15 Feb HW #4 Solution PDF (HMC only) HW #4 Solution IPYNB (HMC only)	BFS Section 2.3 Alon Section 1.3 PBoC: Extracting gene expression from microscopy images week4_hill_functions.ipynb week4_hill_functions.pdf
Week 5 15 Feb 17 Feb	From Processes to Circuits - I Simple Biological Circuits Introduction to Feedback Systems Dynamical System Analysis	HW #5 (PDF) HW #5 (IPYNB) Out: 15 Feb Due: 22 Feb HW #5 Solution PDF (HMC only) HW #5 Solution IPYNB (HMC only)	Toggle Switch in E. coli Repressilator in E. coli week5_feedback_systems.ipynb week5_feedback_systems.pdf PBoC Ch 19: Stability Analysis of the Genetic Switch
Week 6 22 Feb 24 Feb	From Processes to Circuits - II Gene Regulatory Networks Design Principles of Gene Regulation	HW #6 (PDF) HW #6 (IPYNB) Out: 22 Feb Due: 1 Mar HW #6 Solution PDF (HMC only) HW #6 Solution IPYNB (HMC only)	PBoC Chapter 19 Paper: Negative Autoregulation Paper: Eukaryotic Transcriptional Control week6_system_analysis.ipynb week6_system_analysis.pdf
Week 7 1 Mar 3 Mar	Dynamical System Tools for Biological Circuits Introduction to Stochasticity in Biology Simulation of Stochastic Systems	HW #7 (PDF) HW #7 (IPYNB) Out: 1 Mar Due: 8 Mar HW #7 Solution PDF (HMC only) HW #7 Solution IPYNB (HMC only)	BFS Ch. 4 Section 4.1 - CME and RRE BFS Ch. 4 Section 4.2 - Simulation Stability of NAR: Paper on stability of negative autoregulation Gene Expression Noise: Paper on stochastic noise in gene expression week7_stochastic_systems.ipynb week7_stochastic_systems.pdf
Week 8 8 Mar 10 Mar	Biological Circuit Motifs and Systems Feedback Loops Feedforward Loops From circuit motifs to functions	No Homework: Spring Break	Alon Ch. 3 week8_feedforward_loops.ipynb week8_feedforward_loops.pdf
Week 9: Spring Break
Week 10 22 Mar 24 Mar	Modeling Biological Circuits Review: Ordinary Differential Equations (ODEs) Review: Chemical Reaction Networks (CRNs) ODEs for CRNs	HW #8 (PDF) HW #8 (IPYNB) Out: 22 Mar Due: 29 Mar HW #8 Solution PDF (HMC only) HW #8 Solution IPYNB (HMC only)	BFS Ch. 2 week10_compiling_crn_models.ipynb week10_compiling_crn_models.pdf
Week 11 29 Mar 31 Mar	Models for Biological Processes using Python Transcription and Translation Gene Regulation Model Reduction using QSSA and Conservation Laws	HW #9 (PDF) HW #9 (IPYNB) Out: 29 Mar Due: 5 Apr HW #9 Solution IPYNB (HMC only) Repressilator SBML Toggle Switch SBML	Python Packages: Compile CRNs using BioCRNpyler: week11_biocrnpyler_abstraction.ipynb week11_biocrnpyler_dna_assembly.ipynb week11_biocrnpyler_grn.ipynb default_parameters.txt Automated model reduction using AutoReduce: week11_autoreduce_tutorial.ipynb Simulate models using Bioscrape
Week 12 5 Apr 7 Apr	Modeling and Analysis of Biological Motifs Bayesian Inference Robustness and Sensitivity Analysis	Project Proposal Presentations	Python emcee tutorial (IPYNB) week12_bayesian_inference.ipynb Python emcee tutorial (PDF) week12_bayesian_inference.pdf BFS Ch. 3
Week 13 12 Apr 14 Apr	Case Study 1	Project Discussions #1	Arkin et al. "Escherichia coli “Marionette” strains with 12 highly optimized small-molecule sensors". Nature Chemical Biology, 2018. PDF.
Week 14 19 Apr 21 Apr	Case Study 2	Project Discussions #2
Week 15 26 Apr 28 Apr	Summary: Class Review Final Project Presentations	Final Project Reports Due

Grading

The final grade will be based on homework sets and a final project:

Homework (70%): The homework sets every week will comprise of one theory/short-essay/analysis problem and a few programming problems in Python. Each week the problem set will be out after the Tuesday lecture and will be due the next week on Tuesday before the class. You can upload a PDF of your solutions to GradeScope. Collaboration on homework problems is encouraged, please cite all sources in your submission (inlcuding any code snippets used from the Internet, research papers, or discussions with classmates). All homework submissions must be completed by you individually that reflects your understanding of the material.

The best 7 scores out of the 9 homework sets will be used to compute the final score for every student. You can also get 3 free extensions to submit your homework one week later than the due date.

Project (30%): For the final evaluation, each student must work on a project of their choice for the second half of the course. The project will be evaluated on a final report for the project and a short 10 minute presentation during the last week of classes.

Course Resources

The primary resources are the following two textbooks:

[BFS] Domitilla Del Vecchio and Richard M. Murray, "Biomolecular Feedback Systems", 2021. Available Online.
[Alon] Uri Alon, "An Introduction to Systems Biology: Design Principles of Biological Circuits", 2019.
[PBoC] Rob Phillips et al. "Physical Biology of the Cell", Garland Science, 2012.

Additional References:

[CompSysBio] Kitano, Hiroaki. "Computational systems biology." Nature 420.6912 (2002): 206-210.
[HistorySynBio] Cameron, D. Ewen, Caleb J. Bashor, and James J. Collins. "A brief history of synthetic biology." Nature Reviews Microbiology 12.5 (2014): 381-390.
[Repressilator2000] Elowitz, Michael B., and Stanislas Leibler. "A synthetic oscillatory network of transcriptional regulators." Nature 403.6767 (2000): 335-338.
[ToggleSwitch2000] Gardner, Timothy S., Charles R. Cantor, and James J. Collins. "Construction of a genetic toggle switch in Escherichia coli." Nature 403.6767 (2000): 339-342.
[AutoRepression] Rosenfeld, Nitzan, Michael B. Elowitz, and Uri Alon. "Negative autoregulation speeds the response times of transcription networks." Journal of molecular biology 323.5 (2002): 785-793.
[EukaryoticTranscription] Kornberg, Roger D. "Eukaryotic transcriptional control." Trends in biochemical sciences 24.12 (1999): M46-M49.
[StabilityNAR] Becskei, Attila, and Luis Serrano. "Engineering stability in gene networks by autoregulation." Nature 405.6786 (2000): 590-593.
[GeneExpressionNoise] Elowitz, Michael B., et al. "Stochastic gene expression in a single cell." Science 297.5584 (2002): 1183-1186.