LS50: Integrated Science
Course overview
LS50 is a twosemester, double course that introduces the natural sciences as an integrated whole. Its goal is to teach students how to solve scientific problems by drawing methods and concepts from biology, chemistry, physics, and mathematics. The course uses examples from biology as an integrating theme, principles from physics and mathematics to reduce complex problems to simpler forms, and computer simulation to allow students to develop their intuition about the behavior of the dynamical systems that control the physical and biological universe. Each semester will include a project lab, in which students will work in small teams to do original research on unsolved biological problems.
Natural science is a single intellectual enquiry into the universe of objects that surround us. Its components are linked by a common method: inducing hypotheses from a mixture of data and intuition, deducing predictions, and testing them by experiment and observation. The sciences depend on mathematics, from the simple act of counting to sophisticated methods required for computational chemistry and theoretical physics. The Integrated Science curriculum will introduce motivated freshmen to the concepts and methods needed to attack the life sciences in the 21^{st} century. For both semesters, students will take the equivalent of two courses, meeting for formal instruction every day, performing handson, original research, and using modern computer methods to simulate scenarios and analyze data.
Darwin and Wallace's theory of evolution revealed that living things have a purpose: their structure, function, and behavior are integrated to leave as many progeny as possible. For much of the 20^{th} century, this difference, and the astonishing diversity of form and function, tended to separate biology from the other natural sciences: biology's complexity made it unappealing to many mathematicians, physicists, and chemists, and the "assume a spherical cow" flavor of theorists’ simplifying assumptions made biologists skeptical about how useful theory was for understanding biology. Two advances have pushed biologists towards theorists and computer scientists: the need to test our understanding of biological processes by making explicit, mathematical models and the need to convert large datasets into information and, ultimately, knowledge.
We teach students that the answer to “How will you solve this problem?” is “By any means necessary!” Our goal is to teach them how to find interesting problems, the means to solve them, and above all, the knowledge and courage to invent the new methods that make previously insoluble problems soluble. Coupling concepts and methods to problems that excite students and making them use these tools in their own research will embed the concepts in their working memory.
We teach through iterated cycles of experiment and analysis, making use of experimental computation to simulate a system of interacting entities and explore the effect of parameter variation on the system’s properties. Our goal is to complement the formal derivation of theorems, show the productive interplay between theory, simulation, and experiment, and show that computer systems and programs, like biological objects, have purposes. Mastering a restricted syntax to write algorithms will help students think about how biological systems use the restricted syntax of chemistry and genetics to accomplish tasks. Concepts like modularity, exploration with selection, error detection and correction, and recycling previous inventions are important in the function and evolution of both organisms and code. Five faculty will teach the course, working in pairs of one life scientist and one physical scientist.
Students will use their knowledge to conduct original scientific research. The project labs will be based on the research of and run by faculty, a College Fellow, and/or JHDSF Fellows, independent scientists who spend five years at Harvard after their PhDs and run small research groups. We assume don’t assume that students have any prior experience in scientific research.
Class format
All material will be recorded and available over Zoom
Synchronous activity: M, Tu, W, Th, F from 10:3011:45 am, via Zoom. We will use a mixture of two formats, depending on the instructor:
Flipped classroom: lecture material will be prerecorded, will include problems to think about, students will watch the prerecorded material before the flipped classroom and be assembled into small groups to work on problems and discuss them with the instructors.
Synchronous lecture: Material will be delivered over Zoom, with live interactions with students
Midterms: Three 75 minute midterms each semester. Each midterm covers the preceding month’s worth of lecture material. We provide formula sheets and students may create a single, 8.5 x 11 inch cheat sheet with material that they think will be useful.
Final: Threehour final. All problems on the final will be modified versions of problems that appeared on either a problemset or midterm.
Mostly Spring term: Wednesday activities, W, 10:3011:45 am. These will be of various types, including lectures on faculty and teaching fellow research and discussions about careers.
Weekly discussion sections with teaching fellows, at times to be determined based on student availability.
Weekly problem sets, to be submitted as indicated on each assignment. Problem set sessions, a gathering of students with teaching fellows and course assistants to provide advice on tackling problems will be held each week.
Researchbased laboratory: students work on original research projects in small groups. Students are expected to spend 36 hr/week working on their projects. Labs will meet at times to be determined, probably Tuesdays and Wednesdays from 14:00 pm (students choose which day they’ll attend). Fall term: computational biology with Sergey Ovchinnikov. Spring term: bacterial membrances andmechanisms of antibiotic resistance with Emma Nagy.
Faculty
Ben de Bivort  OEB 
Michael Desai  OEB 
Aravi Samuels  Physics 
Andrew Murray  MCB, Course Head 
Emma Nagy  College Fellow 
Cara Weisman  Biophysics 
The yearlong course will be divided into thirds, each teamtaught by a pair of faculty, one from the physical and one from the life sciences.
Laboratory Heads
Sergey Ovchinnikov  John Harvard Distinguished Science Fellow 
Jett Crowdis  Python Bootcamp 
Emily Nagy  College Fellow 
Teagan Stedman  Lab Assistant  Fall Term 2020 
Zoe Weiss  Lab Assistant  Fall Term 2020 
Teaching Fellows
Emma Nagy  College Fellow  Early fall 
Kristin Qian  Department of Medical Sciences  Early fall 
Anastasia Repouliou  MCB  Late fall 
Rui Fang  MCB  Late fall 
Yuan Fang  Systems Biology  Early spring 
Bill Jia  Systems Biology  Early spring 
Tanush Jagdish  Systems Biology  Late spring 
Shreyas Gopalakrishnan  MCB  Late spring 
Syllabus
Below we list the topics covered, weekbyweek for the fall and spring semesters. Since the course will meet every day for two semesters, it will have roughly 100 lectures. As a result the description below is brief and lists weekly topics rather than those of individual lectures. A full schedule is on the course website.
Fall Week 
Topics 

Prewatch Introduction & course overview during shopping period 
1 
Biology as computation. Central Dogma. Inferences, rules, errors. Equilibrium, energy, and steady state. 
2 
Probability and Bayesian analysis. Computation & sequence analysis. Quantization, elements, atomic orbitals. 
3 
Periodic trends, molecular orbitals. VSPER, molecular orbitals and organic molecules. Computation & sequence analysis. Protein structure, intermolecular forces. 
4 
Macromolecules and membranes. Remembering calculus. Computation & sequence analysis. 
5 
Dynamical systems. Computation & sequence analysis. 
6 
Dynamical Systems. EXAM 1. Lac operon. 
7 
Intro to Thermodynamics. Structure. 
8 
Entropy and temperature. Boltzmann Factor and partition function. Structure. Pressure and volume, free energy. Chemical potential. 
9 
Structure. Chemical potential. Chemical reaction equilibria, law of mass action; pigments. 
10 
Cooperativity from a statistical mechanics perspective. EXAM 2. Cooperativity from a biochemical perspective. Intro to diffusion 
11 
Chemotaxis. Diffusion and chemical potential. Examples of diffusion 
12 
Chemotaxis. Diffusion limited reactions. Membranes, channels and pumps. Mechanisms of enzyme catalysis. Photosynthesis and redox. 
13 
Mechanisms of enzyme catalysis. Chemiosmotic hypothesis and ATP synthase. THANKSGIVING! 
14 
EXAM 3. 
Spring schedule to be added soon
Matlab/Python
We assume no prior experience in writing computer programs, but a major goal of the course is to teach scientific computation, using the language Matlab or Python. Unless they have previous experience with Matlab or Python, students will participate in a boot camp run by Adam Cohen and colleagues (Matlab) or Sergey Ovchinnikov (Python). Example of information can be found here: https://wiki.harvard.edu/confluence/display/fasmatlab (you need a Harvard key to access).
Problem sets will have questions that depend on your ability to use Matlab/Python, but we will increase their difficulty gradually so as not penalize those encountering a computer language for the first time.
Assessment
Assessment will be based on five criteria:
Inclass tests & Final exam
We will administer three inclass tests, each 75 min long and each covering the material presented in the preceding month. The question format and content will be similar to the weekly problem sets. Students can bring a singlesided 8.5 x 11 inch piece of paper, with any information they wish to remember to each exam and we will provide a sheet with key formulae and equations.
Final Exam  A threehour final. All problems on the final will be modified versions of problems that appeared on either a problemset or midterm.
Problem sets
Weekly problem sets will review the topics covered in lectures and discussion sections. We strongly encourage students to collaborate to solve the problems, which may include a comparison of scratch work, methods used, and numerical results. All submitted work should be written independently and reflect the students’ own understanding. Students should not submit work that they would be unable to explain or reproduce on their own.
This policy reflects our intent in assigning the problem sets: to help you master the material under lowstress circumstances so you will not be blindsided by higherstakes tests. While you should be wary of overreliance, classmates are an excellent resource for help since they keep similar hours, live nearby, and remember their own learning process well enough to explain concepts appropriately. On the flip side, mentoring colleagues whenever possible is not merely kind and forwardthinking, but also helps crystallize your understanding and practice the mentorship and presentation skills needed for work in the scientific community.
Laboratory research
Students will be graded on the research projects they undertake, focusing on their ability to design and interpret experiments and their commitment to and engagement with their research more than on the quality of the results they produce (subject as these are to the whims of the Gods). Approximately half of the grade from laboratory research will reflect weekly participation in lab, with the remainder attributed to a final lab report.
Participation
Students will be graded on their participation in class, which we expect to be highly interactive, weekly conferences, and the discussions associated with laboratory research.
These criteria will be accorded the following weights:
Exams  40% 
Problem sets  30% 
Laboratory research  20% 
Participation  10% 