Scientific Foundations Syllabus

Contact Information

Director - Dr. Pete Takizawa

Discipline Leads

• Biochemistry - Dr. Susan Baserga
• Cell Biology - Dr. Pete Takizawa
• History of Medicine - Dr. Joanne Radin
• Pathology - Dr. Roxanne Wadia
• Pharmacology - Dr. Ben Turk
• Pharmacology - Dr. Mike DiGiovanna
• Physiology - Dr. Tore Eid

Important Dates

• Course Starts: Wednesday, August 26
• Self-Assessment: Friday, September 11 through Sunday, September 13
• Qualifier: Friday, September 25 through Tuesday, September 29

Passing the Course

There are three requirements to passing the course:

1. Score 65% or better on the qualifier (see below). If you score below 65%, you must complete remediation to pass the course (see below).
2. Complete the online Health Maintenance module.
3. Complete the health equity reflection.

Qualifier

The qualifier will have about 75 multiple-choice questions and one short-answer question. The passing score is 65%.

Remediation

If you score below 65% on the qualifier, you will need to complete remediation to pass the course. Remediation consists of writing rationales to explain the correct answers for the questions you answered incorrectly. The rationales will be submitted to the course director, who will evaluate your rationales and determine whether they indicate you have demonstrated a sufficient understanding of the course materials to pass the course.

Formative Assessment

Formative assessment consist of weekly quizzes and a self-assessment midway through the course. These are designed to give you a sense of how well you understand the material in the course and your ability apply the material to clinical problems. Summative feedback consists of a qualifier at the end of the course.

Where to Get Help

It is not uncommon for students to struggle in this or other courses. If you encounter difficulty learning the material, you can contact the Course Director to set up a meeting to find ways to help you navigate the course. Also, the Discipline leaders are available to answer question about content in their Disciplines. Student Affairs has a learning specialist, Andrea Giampetruzzi, who can meet with you to discuss effective ways to learn and keep current with course content.

Course Goals

Scientific Foundations aims to instill in students a firm understanding of the basic principles in molecular biology, cell biology, physiology and pharmacology that will serve as a foundation for your subsequent education and development as physician-scientists.

Course Learning Objectives

• Demonstrate sufficient knowledge of the fundamental concepts in the disciplines (see list below) covered in the course. 
• Use knowledge of the fundamental concepts (see list below) to describe disease processes and identify biochemical, cellular and physiological causes of symptoms in clinical cases. 
• Demonstrate basic knowledge of the scientific basis and evidence supporting recommendations for common health promotion and disease prevention strategies.
• Begin to identify biases in the way medical knowledge is generated or interpreted and how these biases affect patient care. 

Fundamental Concepts

Biochemistry 

1. Mechanisms and regulation of gene expression, protein function and concentration: transcription, RNA processing, translation, folding, localization, modification, and degradation. 
2. Pathways and key enzymes that convert macromolecules in food to usable energy currency (ATP, NADH, NADPH) and dispose of carbon and nitrogen waste. 
3. Integration of metabolic systems that maintain energy balance and distribute energy-rich molecules. 
4. The pathways and key enzymes that generate the building blocks of macromolecules (amino acids, nucleotides and fatty acids). 

Cell Biology 

1. Structural and functional components of cells and extracellular matrices 
2. Structures and functions of major tissue types: epithelia, muscle, connective and nervous 
3. Structures and functions of different types of blood vessels 
4. Vectorial transport of solutes and water across epithelia 
5. Molecules, pathways and connections that mediate cell communication 
6. The basic pathways and mechanisms that regulate cell division and tissue renewal 

Embryology 

1. Development of the trilaminar disc from a fertilized ovum 
2. Development of the neural tube 
3. Segmentation and development of the gut tube 
4. Development of pharangeal pouches 

Pathology 

1. Cellular adaptation to stress and injury 
2. Programmed cell death (apoptosis) and necrosis 

Pharmacology 

1. How drugs alter receptor activation 
2. Availability, distribution, clearance and efficacy of drugs in patients 
3. Identification and initial development of novel drugs 

Physiology 

1. Volumes and composition of the fluid compartments in the body and how fluids move between compartments 
2. Generation and maintenance of membrane potential 
3. Solute transport across biological membranes 
4. Initiation and propagation of action potentials 
5. Electrical pathways in muscle contraction

Teaching Methods

Scientific Foundations uses lectures, small-group sessions, labs and team-based learning to deliver content and develop your critical-thinking skills.

Lectures

Lectures will present the essential concepts and illustrate the how these concepts inform medicine and our ability to diagnose and treat disease. Most lectures will be delivered asynchronously through short videos. A few lectures will be in person, and these will be recorded for you to review.

If you have to miss a lecture, please try to watch the podcast of the lecture the same day it was given. Many of the small-group sessions assume that you are familiar with the content presented in the preceding lectures, and if you haven’t attended or watched a lecture, you will not be able to contribute to the discussion in small group and fully develop your critical-thinking skills.

Case-Based Workshop

Case-based Workshops offer you an opportunity to work through a clinical case in a small-group setting and under the guidance of a faculty member. Cases have been chosen to allow you to apply what you have learned in lecture to uncover and understand the mechanisms of a specific disease. Case-based workshops will focus on topics related to biochemistry and physiology.

Team-based Learning

Team-based Learning (TBL) delivers content and allows students to apply what they’ve learned to solve real-world problems. TBL employs a flipped curriculum in which you learn content before coming to class and then use in-class time for active learning and problem-solving. In class, you will work in a team to answer questions and solve problems. For more information on TBL, please Read More.

Test-enhanced Learning

Test-Enhanced Learning combines acquisition of knowledge and application of knowledge in a single session. The first part of a test-enhanced learning session consists of a short lecture and the second part is an interactive session in which students work on questions usually similar to those seen on Step 1 exams.

Online Pharmacology Module

The Pharmacology Discipline has developed an online curriculum that describes how new drugs are discovered, tested and then reviewed. The online curriculum was developed in collaboration with Merck Pharmaceuticals and is the divided into five modules:

• How Drugs are Discovered
• Consideration for Testing a Drug on Humans
• How Investigational Drugs are Tested in Humans
• Regulatory Review Process for New Drugs
• Post-Approval Activities
• Principles of Vaccine Development and Clinical Vaccinology

In Scientific Foundation, we ask that you complete the first two modules before September 18. On that date, there will be an in-class discussion of the content in the first two modules. If you have any questions about the online Pharmacology modules, please contact Dr. Mike DiGiovanna at michael.digiovanna@yale.edu.

How the Course is Organized

Scientific Foundations presents the foundational material from several disciplines that are the pillars of biomedical science and medicine. These include Biochemistry, Cell Biology/Histology, Pathology, Physiology, and Pharmacology. Each of these disciplines will continue throughout the pre-clerkship curriculum where they are called Disciplines because of the way their content is woven into the courses across the pre-clerkship curriculum. Scientific Foundations will present the core concepts and introduce the modes of thinking that are essential for each of these Disciplines.

When you draw on your biomedical knowledge to analyze a case, the relevant information usually doesn’t come from only one discipline. Instead, you will often integrate information from several disciplines. For this reason and others, the content from the Disciplines covered in this course has been integrated into themes that reflect important biomedical processes:

• Building a Body
• Fluids and Gradients
• Gene Expression
• Cell Energy
• Cell Communication
• Life and Death of a Cell

Themes

As multicellular organisms we have evolved a developmental program (which will be described in Genes and Development) that generates structures - our organs and tissues - which perform specific functions to increase our chances of survival and reproduction. Disease often arises when one or more of our organs alters its normal behavior or fails to perform one of its essential functions. To understand why organs and tissues stop working properly, we turn to biomedical science, which operates under the paradigm that to understand the whole we must learn how the individual parts work and interact with each other. Thus, to understand how organs and tissues work and occasionally fail to work, we need to study their structural and functional parts. All organs and tissues are composed of cells and material produced by cells, which work in concert to generate the life-supporting functions of each organ and tissue. Thus, cells are the fundamental units of life and understanding how they work in tissues and organs is key to learning the biological causes of disease. The themes in the course center on cells and their roles in supporting critical life processes and development of disease.

Building a Body

Building a Body describes the molecular interactions that generate functional cells and allow cells to assemble into tissues and organs. Building a Body examines the component parts of cells, such as DNA, RNA, protein, lipid and carbohydrate, and describes how these macromolecules are organized to form cells. Next, we will explore the interactions between cells and the external macromolecules produced by cells assemble into functional structures called tissues. The body contains four types of tissues: epithelia, muscle, nervous and connective. Organs are composed of a mix of these tissues (and other types of cells) that generate a structure capable of performing several functions. Thus, Building a Body will trace the chain of interactions from molecules to cells to tissues and organs. Along the way, we describe diseases which arise due to small changes at the macromolecular level and compromise the function of tissues and organs.

Fluids and Gradients

By weight, half or more of our bodies are composed of water. This water is distributed into three main fluid compartments: blood, inside cells, and surrounding cells. These fluids in these compartments contain the solutes that are essential for life: proteins, nucleic acids, molecules, ions, etc. But life depends upon reactions and interactions, which means these solutes need to find each other. Fortunately, thermal energy generates diffusion which mixes the solutes, but concentrating specific solutes within a compartment, especially inside the tiny volume of a cell, facilitates reactions and interactions.

Fluids and Gradients describes the volumes and solute composition of these compartments and how the body maintains these volumes and regulates movement of solutes between compartments.

Keeping the main fluid compartments at appropriate volumes is critical. If the volume of a cell rapidly shrinks or expands, it can lead to cell death. An increase in the volume of fluid in the circulatory system leads to high blood pressure which can cause several diseases.

Solutes must also move between compartments. Nutrients must enter cells from the fluid outside, while waste must be excreted from cells into surrounding fluid. Communication between neurons and the beating of the heart depend on the movement of specific ions into and out of cells.

The theme will explain all these events and allow you to apply your knowledge to clinical cases where these events have changed.

Gene Expression

Although the cells in our bodies are composed of four different types of macromolecules, proteins and to a lesser extent RNA drive most of the reactions that are critical to the function and survival of cells. The concentration and location of proteins within cells determines the rates of these reactions and whether the cell is normal, dying or dangerous. In addition, each type of cell in the body expresses a unique combination of genes which allow them to perform specific functions and maintain their identity and location. Changes to that gene expression profile can lead to aberrant behavior, including loss of normal function or gain of inappropriate function, both of which can lead to disease. This theme will describe the steps that produce a protein from a gene and describe the mechanisms that regulate the rate of protein production.

Once a protein is synthesized its ability to catalyze a reaction depends upon whether it folds into a correct three-dimensional structure and finds its reactants. The theme will describe the basic process of protein folding and how cells facilitate protein folding. Proper folding is not only important to generate functional protein but also for the health of the cell. Accumulation of unfolded protein can lead to cell death and is thought to be the cause of several diseases, including Alzheimer’s.

Energy and Metabolism

Many reactions and molecular events require an input of energy to proceed. Our cells obtain energy from the chemical bonds in the molecules that compose the food we eat. Because of the diversity of molecules in our food and the large number of different enzymes that require energy for their reactions, cells have evolved to use a common currency to exchange energy stored in food molecules and consumed by enzymes: ATP. This theme describes how cells convert macromolecules in food into ATP. The theme reveals how the pathways that lead from macromolecule to ATP are regulated and the benefits to cells of using one pathway versus another.

Because cells in the different organs and tissues vary in their energy needs, our bodies need a global energy policy to maintain a sufficient distribution of energy-rich molecules throughout our body and to create an adequate reserve supply of energy for when demand increases. Several homeostatic mechanisms control the concentration of energy-rich molecules in the circulatory system and the storage of energy as fat and carbohydrate. Breakdown of these mechanisms can lead to chronic diseases such as diabetes and cardiovascular disease.

In addition to energy, our cells need an ample supply of macromolecules, such as amino acids, nucleotides, sugars and lipids, that are the building blocks of essential large molecules and structures. While some of these building blocks are obtained through our diet, cells can also synthesize many of them to ensure they have an adequate supply.

Information and Communication

We are multicellular organisms composed of trillions and trillions of cells. Over 200 different types of cells are organized into tissues and organs. To produce a functioning organism, cells in the different tissues and organs must work in a coordinated fashion. Coordination requires communication and this theme will explore how cells communicate with each other, often between distal parts in the body.

Communication requires a language or a way to convey information. The cellular language is frequently encoded in small molecules that are produced by cells and detected by other cells. Thus, small molecules are like words to cells, and cells must distinguish between small molecules to know how to respond. This theme will explore how cells identify a specific molecule and the pathways that connect a specific molecule to a change in cell behavior.

With an understanding of how cell communication works, the theme will reveal how science and medicine have developed small molecules to manipulate the activity of cells either to treat a disease or reduce its symptoms. The basic mechanisms of action of drugs will be described as well as the way the body processes those drugs.

Life and Death of a Cell

All cells have a limited life span which is often determined by their exposure to the environment. As multicellular organisms, we need a way to replace dying cells so that our organs and tissues continue to function properly. In many organs and tissues, stem cells differentiate and divide to generate new cells that can replace old or dead cells. Importantly, the rate of cell division in a tissue or organ must closely match the rate at which cells are lost. If the rate of cell division is too fast, it leads to overgrowth of cells and can compromise the structure and function of a tissue or organ. Rapid cell division is also increases the risk of development of a tumor.

This theme will describe the mechanics of cell division and then list the pathways and regulatory elements that control the rate of cell division. The theme will also introduce how mutations in regulatory factors lead to the development of tumors.

Cells are also occasionally subjected to physical, chemical and even electrical trauma that causes damage. How they respond to these injuries determines whether cell survives, dies or becomes pathologic. The second part of this theme will show how cells respond to injury and try to repair themselves. The theme will also discuss what happens to a cell when the damage is too much to repair and how cells can die without causing damage to surrounding cells. Lastly, the theme will demonstrate the pathological effects of large scale damage to cells and tissues.

Learning Units

The course will be organized into four learning units each corresponding to a week in the course (the first unit will span 1.5 weeks as the course starts on a Wednesday). Each learning unit will try to group related content. A learning unit will start with a session that introduces the topics for that week, how you will acquire knowledge about those topics, and how you apply that knowledge to reason through clinical problems and understand the mechanisms of specific diseases. A learning unit will end in a session to help you consolidate what you have learned during that week.

Learning Unit One: Tissues

Most of the organs and structures in the body are composed of four tissue types: epithelia, muscle, nervous, and connective. The main focus of the unit will be the structure and function of those tissues. The unit will start with some basic information about cells and how cells assemble into tissues. Then each of the four tissues types will be covered in detail. The unit will also cover some essential properties common to most cells and tissues. First is protein homeostasis, which are the mechanisms that regulate protein concentration, location, and activity. Second is the movement of solutes and fluids into and out of cells and across tissues, which is essential for cell viability and the activity of tissues.

Learning Unit Two: Energy and Metabolism

Our bodies get energy from the molecules in the food we eat, but the energy in this molecules must be converted into form that is useable by cells. The unit will lay out the pathways that cells have evolved to convert the carbohydrates, proteins, and lipids to ATP, handle waste from those pathways, and store energy for future use. The unit will also describe how cells make the subunits (amino acids for the essential macromolecules. The unit will also explore how these pathways are coordinated in tissues and organs across the body to maintain an energy balance and adapt to changes in resources to sustain life.

Learning Unit Three: Information and Communication

The focus of this unit will be the mechanisms through which cells communicate across the body. Many important physiological parameters, such as blood pressure, are controlled by different tissues and organs in the body. Proper setting and regulation of these parameters requires communication between cells in different parts of the body. The unit will describe the molecules and pathways that mediate communication and how drugs can be used to affect these pathways to restore physiological parameters to normal or fight a specific disease. The unit will also describe how the body absorbs, distributes, detoxifies, and excretes drugs.

Learning Unit Four: Life and Death of a Cell

Francois Jacob wrote “the dream of every cell is to become two cells”. This unit will describe the process through which one cell divides into two and how tissues regulate cell division to ensure that they replace old and dying cells with new ones. The unit will also explore how cells and tissues respond and adapt to changes in their environment, and when no longer viable, undergo an ordered cell death to preserve tissue integrity.