Week 1 Cohort 1 Cell Structure and Function PDF

10.019 Science and Technology for Healthcare Week 1 Cohort 1: Course Introduction Introduction to Stem Cells Cell Structure and Organization  A Warm Welcome to 10.019! Dr. Chandrima Dr. Hendrikje Werner- Dr. Lou Xuanming...

10.019 Science and Technology for Healthcare Week 1 Cohort 1: Course Introduction Introduction to Stem Cells Cell Structure and Organization  A Warm Welcome to 10.019! Dr. Chandrima Dr. Hendrikje Werner- Dr. Lou Xuanming Dr. Tan Mei Xuan Chatterjee Saerbeck Lecturer, SMT Senior Lecturer, SMT Senior Lecturer, SMT Adjunct Fellow, SUTD (Ph.D., Mechanobiology) (Ph.D., Integrative (Ph.D., Biophysical (Ph.D., Molecular Sciences & Engineering) Chemistry) Biotechnology) Copyrights 2  Course Aims and Expectations Why Study Biology? 1. As Creators of biomedical technology 2. Towards healthtech or medtech Careers 3. As Collaborators with clinicians and biologists 4. As Citizens who use biology in health decision-making 5. As Consumers who apply their biology knowledge to making better product choices 6. As Critics of the misuse of biology 7. As Connoisseurs who enrich their lives with science Copyrights Adapted from Robin Millar, Uni of York 3  Course Aims and Expectations Our Personal Goal For You “SCIENCE LITERACY” To be curious about human biology and health and appreciate that living systems are complex but fascinating To be able to make hypotheses and design appropriate solutions to healthcare problems To understand that biology is also about problem solving and applying information, and not just memorizing facts Copyrights Adapted from MITOCW 4  What will you learn in this course? 10.019 Science and Technology for Healthcare (ST4H) (greater emphasis on molecular and cell biology fundamentals which form the the basis of human health and disease) Copyrights Silverthorn, Human Physiology, Fig. 1.1 5  Course Learning Objectives This course is for students who would like a better understanding of leading chronic diseases and the limitations in their diagnosis and treatment. At the end of the course, students will be able to apply fundamental biology knowledge to better appreciate current technologies and pressing challenges in healthcare. Overall Learning Objectives 1. Apply fundamental concepts in molecular biology (DNA and genes), cell biology and human physiology to compare and contrast function and regulation in the healthy versus diseased states. 2. Apply fundamental concepts of classical and modern genetics towards the understanding of the patterns of human inheritance and clinical manifestations of genetic diseases. 3. Interpret and analyze common experimental data (both qualitative and quantitative) derived from molecular biology and genetic tests. 4. Research and discuss factors that need to be considered in the prevention, early detection, and treatment of cancer. Copyrights 6  Course Format Two 2.5h cohort class sessions Mini-lectures, group discussions, and hands-on activities In-class worksheets Pre-class Video + Weekly MCQ (Flipped; on eDimension) Weekly MCQs must be submitted by Monday at 9:00am, before the cohort lesson that week Essential content for cohort class will not be retaught in cohort; pre-class content will be tested Weeks 1, 2, 3, 5, 8, 10, and 11 To further support your learning: Midterm Quizzes and Finals Quiz 1 (Week 4) Progressive Learning Sessions (PLS) Quiz 2 (Week 9) When: Weekly on Fridays @ 2 – 4 pm Final Exam (Week 14) Where: Cohort Classroom 14 (2.507) What: Weekly summary notes + Group Projects practice problems + consultation 1D Lab (Week 4) 2D Project (Week 12) Instructor Consultations Week 13 Presentations Email for appointment Weekly Homework Due Wednesdays 5pm (online Gradescope submission) 6 homework assignments (3% each) No submission for Week 3 and Week 8 (due to quiz in following week), and Week 11 Homework Copyrights 7  Monday Schedule (2 pm – 3 pm) Week(s) Description Location Details Weekly Pre-Class (Flipped): Videos and MCQ released one week before 1, 2, 3, 5, Self-study Pre-class Videos E.g., Week 3 videos and MCQ released in Week 2, and 8, 10, 11 (own place and time) MCQ Quiz (eDimension) due on Monday 9am at the start of Week 3 Oct 21: Diabetes Distinguished Clinician Lecture In-person Dec 2: Infectious Disease 6, 12, 13 (CGH Guest Lectures) LT2 (1.203) Dec 9: Cancer Attendance is mandatory and will be recorded; Respective cohort 4, 9 Midterm Quizzes 1 and 2 Oct 7, Nov 11; Quiz will begin promptly at 2pm classrooms Copyrights 8  Course Assessments Midterm Quiz 1 (10%) – Week 4 Physical venue: Cohort classrooms Content from Weeks 1, 2, 3 Bring your own laptops; Closed book; Multiple-choice questions (MCQ) Midterm Quiz 2 (10%) – Week 9 Physical venue: Cohort classrooms Content from Weeks 5, 6, 8, but may require concepts learned earlier in the course Bring your own laptops; Closed book; Multiple-choice questions (MCQ) Final Exam (25%) – Week 14 Physical venue: TBD (centralized) Content from Weeks 8, 9, 10, 11, but may require concepts learned earlier in the course Hardcopy exam; 1 A4 double-sided cheat sheet; Both Multiple-choice AND Structured questions Copyrights 9  Weekly Homework Homework for Weeks 1, 2, 3*, 5, 6, 8*, 9, 10, 11* (Week 3, 8, 11 not collected – due to midterm and 2D) Total 6 graded homework Submit online through Gradescope by Wednesday 5pm of following week Please contact your cohort instructors if there are any issues Copyrights 10  Overall Grade Breakdown Assessments Grade Final Exam 25% Midterm Quizzes x 2 20% Weekly Assignments (25%) Homework x 6 18% Pre-Class MCQ x 7 7% Class Participation (10%) Week 13 Group Presentation 5% Guest Lecture Attendance 3% End-term course evaluation survey 2% 1D Project 10% 2D Project 10% TOTAL 100% Late penalty: Grade of 50% if within 24h and 0% if > 24h from due date Please notify instructor of any absences ahead of time (with documentation) Copyrights 11  Course Textbooks Alberts et al., Essential Cell Biology, 4th edition, Garland Science, 2014 Main course text; available at SUTD library and in cohort classroom. Provides a very nice conceptual understanding of the most essential principles; uses simplified, stripped-down illustration Campbell et al., Biology: A Global Approach, 10th edition, Pearson, 2014 Main course text; available at SUTD library and in cohort classroom Highly detailed and comprehensive text densely packed with information. Figures are very detailed and clear with informative captions. Copyrights 12  Supplementary Text Pre-class Reading: In order to get maximum benefit from the lessons, you are strongly encouraged to complete the assigned textbook reading before class. Even a superficial first reading the night before will improve your comprehension and retention of the material covered in class and allow for more active engagement in the classroom activities. Clark et al., Biology 2e, OpenStax, 2018 Supplementary, optional resource; free access at https://openstax.org/books/biology-2e/pages/1- introduction Comprehensive but suitable for all levels with simple, straightforward figures and illustrations Copyrights 13  Questions? 14 Copyrights  Week 1: Pre-Class Material Part 1: Cells – The Basic Unit of Life Part 2: Cells and the Chemistry of Life Complete Pre-Class MCQ (eDimension) Due Monday @ 9am Copyrights 15  Week 1 Pre-Class Summary Organisms are living entities comprised of one or more cells Cell is the basic structural, functional, and biological unit of life Cells are varied in appearance and function but share fundamental chemical characteristics The human body has different levels of organization, from simple to complex, small to large Cells are highly complex chemical systems with shared fundamental characteristics Cells are mainly composed of four classes of macromolecules – carbohydrates, lipids, proteins, and nucleic acids Macromolecules are formed and broken down via dehydration and hydrolysis reactions, respectively Cells are very small and composed of complex structures and molecules that can be visualized under the microscope Cellular dysfunction can result in disease Questions on the pre-class material? Copyrights 16  What do you see here? How many different cell types are seen here? Which cell(s) belong to a unicellular organism? Which cell(s) belong to a multicellular organism? What are the cells doing? Credit: David Rogers, Vanderbilt University Copyrights 17  How many cells in the human body? (FYI) There are roughly ___________ cells in the human body. A. 3 million (106) B. 30 million (107) C. 30 billion (1010) D. 30 trillion (1013) E. Similar to the number of atoms in the universe (~1080) Copyrights 18  Recap: The Cell is the Basic Unit of Life The cell is the basic structural, functional, and biological unit (i.e., “building block”) of all known organisms Cells come in very diverse shapes and sizes but share fundamental characteristics in their components Fig. 4.1 OpenStax Biology 2e. From L to R: Human nasal sinus cells (viewed with light microscope), onion cells (viewed with light microscope, and Vibrio tasmaniansis bacterial cells (viewed with scanning electron microscope). The human body is composed of more than 30 trillion cells, with >200 different cell types, each specialized for a specific function Specialized cells of the human body: Copyrights Biology Concepts, LibreTexts 19  Recap: Levels of Organization of the Body (E.g., Cardiovascular System) Copyrights 20  Lesson Outline Introduction to Stem Cells Cell structure and organization – Prokaryotic vs. Eukaryotic cells Mini-Activities: – Visualizing Cells under the Light Microscope – Build a Virtual Eukaryotic Cell (Animal vs. Plant Cell) Copyrights 21  Learning Objectives At the end of the lesson, you will be able to: Describe the various types of stem cells and their varying ability to differentiate into the different cell types of the body Discuss the potential use of stem cells in clinical medicine Explain the difference between eukaryotic and prokaryotic cells Identify the various eukaryotic organelles and briefly describe their normal cellular function Distinguish between an animal and plant cell Copyrights 22  Relevant Readings Alberts et al. Essential Cell Biology, 4th Edition, Garland Science, 2014. Ch 20 Pg. 705 - 712. Lippincott Illustrated Reviews: Cell and Molecular Biology, 2nd Ed, Wolters Kluwer, 2019, Ch 1 Copyrights 23  From Cell to Organism (Credit: Texas Fertility Clinic) Repeated rounds of division of a fertilized egg This newborn baby is composed of more than (zygote) in the early development stage of a 30 trillion cells, with >200 different cell multicellular organism; IVF = in vitro fertilization types, each specialized for a specific function How do we get from the single cell (zygote) to the complex and highly-organized multicellular organism? Cell proliferation = grow + divide Precursor cell Human body with >30 trillion “Stem cell” Cell differentiation = specialize cells with >200 cell types Copyrights 24  Stem cells give rise to the specialized cells of the body Stem cells are undifferentiated or partially differentiated cells that can develop into other specialized cell types Stem cells generate a continuous supply of differentiated cells When a stem cell divides, each daughter cell can either remain a stem cell or go on to become terminally differentiated (i.e., fully specialized; unable to develop any further) Copyrights Figure 20.35 Essential Cell Biology 25  Cell differentiation (i.e., specialization) – When a cell becomes more specialized in structure and function – This happens through a process of selective gene expression, i.e., turning ON or OFF of specific genes (units of DNA which contains genetic information that relates to an organisms’ traits) Each cell type expresses a different subset of genes, giving rise to specialized cell structure, behavior, and function Only a small subset of all human genes are expressed in each fully differentiated cell A housekeeping gene is a gene required to maintain basic cellular function and so is typically expressed in all cell types of an organism Copyrights 26  Clicker Question In which organ would you expect to find the greatest number of stem cells? Skin - largest organ in the body A. Brain Skin cells are constantly shed and need constant renewal B. Heart C. Skin D. Kidney Copyrights 27  Stem cells play an important role in tissue renewal Example: stem cells in the basal layer of the epidermis continually divide and differentiate into new skin cells to replace those that shed from the top layer Figure 20.37 Essential Cell Biology Copyrights 28  Video – Stem Cells and their Applications Copyrights https://www.youtube.com/watch?v=i2pyDBMglfM 29  Clicker Question Which of the following stem cells would show the greatest capacity to differentiate into other cell types? A. Stem cell from the early embryo B. Stem cell from a newborn baby C. Stem cell from a child D. Stem cell from an adult Plasticity = capacity of stem cell to differentiate into other cell types Copyrights 30  Stem cells have different levels of plasticity Plasticity = capacity of stem cell to differentiate into other cell types Capacity to develop into a total organism Capacity to give rise to all cell types in the body, but not supporting structures, such as the placenta Embryonic stem cells (ESCs) isolated from the blastocyst inner cell mass are pluripotent Capacity to give rise to multiple different cell types Adult stem cells are found in small numbers in various tissues in the body. They are multipotent or unipotent Capacity to give rise Unipotent to only one cell type Copyrights 31  Clicker Question From which type of stem cells might it be possible to obtain tissue to regenerate brain function in a patient suffering effects of a severe stroke? Select ALL possible options: A. ESCs from inner cell mass B. Hematopoietic SCs C. Neural SCs D. Mesenchymal SCs Copyrights 32  Multipotent stem cells differentiate within a specific lineage Example: a hematopoietic stem cell (HSC) divides to generate more HSCs, as well as precursor cells that proliferate and differentiate into all the various cells of the blood. HSCs are unable to differentiate down a different lineage i.e., cannot become muscle cell Figure 20.39 Essential Cell Biology Copyrights 33  Clinical Application: Blood Stem Cell Transplants Technically a hematopoietic stem cell transplant (HSCT) 3 different types, based on cell source: – Bone marrow transplant  HSCs from bone marrow – Peripheral blood transplant  HSCs from whole blood – Cord blood transplant  HSCs from placenta and umbilical cord Credit: Cordlife Copyrights 34  The Promise of Embryonic Stem Cells (ESCs) Pluripotent ESCs could serve as a renewable source of replacement cells and tissues to treat several diseases and conditions, including: Type 1 diabetes, where the beta + appropriate cells of the pancreas are chemical and destroyed physical cues Stroke, where a blood clot causes oxygen deprivation and loss of brain tissue. Spinal cord injuries, leading to paralysis of skeletal muscles. Other conditions such as burns or heart disease, osteoarthritis What are some concerns about Human clinical trials are ongoing across several countries the use of embryonic stem cells? Copyrights 35  The Embryonic Stem Cell Debate (FYI) Medical or scientific issues - Are ESCs the best stem cells for regeneration and repair? - Are there any medical risks inherent in the use of ESCs? Ethical issues - What is the source of embryos? - When is an embryo or fetus considered a living person? - What legal status, if any, does an embryo have? - Who has the right to use the harvested stem cells? There are many laws and acts which researchers are legally bound by. Must have special license to carry out research on embryos Can only use “excess” embryos (e.g., leftover from IVF) Must have written permission from individual responsible for embryo Embryos cannot be created for research purposes Copyrights 36  If not human embryos… then what are some alternative sources of pluripotent stem cells? Copyrights 37  Alternative Sources of Pluripotent Stem Cells 1) Therapeutic cloning (i.e., somatic cell nuclear transfer) Essential Cell Biology, 4th ed 2) Induced pluripotent stem cells (iPS cells) four Beating heart muscle cells derived from iPS cells Copyrights Credit: Zhen Ma et al., Nature Communications 38  Video – Making Induced Pluripotent Stem Cells (iPSCs) https://www.youtube.com/watch?v=2zoLUmZyxLk Copyrights 39  Clicker Question Induced pluripotent stem cells (or iPSCs) involve the: A. Activation of stemness in embryonic stem cells B. Generation of cells from the inner cell mass of blastocysts C. Conversion of a totipotent cell to pluripotency D. Reprogramming of unipotent cells to be pluripotent Copyrights 40  Clinical Applications: Cell Source for Tissue Engineering (FYI) Modified from Anaïs Chalard, 2019 or iPSCs Tissue Engineering Approach Tissue graft (injectable or transplantable) Appligraf is a bovine type I collagen matrix cultured with allogeneic male neonatal fibroblasts and keratinocytes Multiple cell types and supporting structures needed for Copyrights a fully functional skin substitute Metcalfe A., J. Royal Society Interface 2006 Simon Myers et al. Tissue Engineering, 2014 41  Summary: Introduction to Stem Cells Stem cells are undifferentiated or partially differentiated cells that can develop into other specialized cell types Stem cells exist in embryos and in adult tissues Differentiation involves the turning on/off of specific genes Plasticity refers to the ability of a cell to differentiate into different cell types Stem cells have varying extents of plasticity (totipotent, pluripotent, multipotent, unipotent) Pluripotent SCs can give rise to all cell types and show great potential for use in regenerative medicine Induced pluripotent stem cells (iPSCs) generated from adult somatic cells are a promising source of stem cells Copyrights 42  Lesson Outline Introduction to Stem Cells Cell structure and organization – Prokaryotic vs. Eukaryotic cells Mini-Activities: – Visualizing Cells under the Light Microscope – Build a Virtual Eukaryotic Cell (Animal vs. Plant Cell) Copyrights 43  The Microscopic World of Cells (FYI) Fig. 4.6 OpenStax Biology 2e. Try me! Cell size and scale: Copyrights https://learn.genetics.utah.edu/content/cells/scale/ 44  Visualizing Cells Cells are very small (micron-scale) and composed of complex structures and molecules as visualized under the (A) light microscope, (B) fluorescence microscope, and (C) electron microscope Copyrights 45  E.g., Transmission Electron Microscope (FYI) Prokaryotic cell Eukaryotic cell Copyrights 46  Mini-Activity: Visualizing Cells w/ Light Microscope Make your way to the microscopes to view the following three types of cells: Human buccal epithelial Onion root tip cells Human Blood Smear (cheek) cells Carolina Biological Supply Red Blood Cells (RBC) http://www.olympusmicro.com White Blood Cells (WBC) Carolina Biological Supply How do these cells differ from each other? How are they similar? Copyrights 47  Classifying Life: Prokaryotes vs. Eukaryotes Living organisms can be briefly classified as Prokaryotes or Eukaryotes Prokaryotes comprise of simple unicellular organisms such as bacteria Eukaryotes include the more complex unicellular or multicellular organisms that we are familiar with, such as plants, animals, and fungi Prokaryotes Unicellular organisms (single-celled) Eukaryotes Multicellular organisms (multiple cells) Copyrights Credit: Archaebacteria: NASA; Bacteria: De Wood and Chris Pooley/Agricultural Research Service, USDA; Protist: Image copyright MichaelTaylor, 2014; Fungus: Tony Hisgett; Plant: Mauro Guanandi; Animal: úlfhams_víkingur 48  Prokaryotic vs. Eukaryotic Cells Lumen Learning Prokaryotic cell (“before nucleus”): a Eukaryotic cell (“true nucleus”): a type of type of cell lacking a nucleus and other cell with a nucleus and many membrane- membrane-bound organelles. bound organelles (“little organ”). Organisms with prokaryotic cells are Organisms with eukaryotic cells are called unicellular and called prokaryotes. eukaryotes. (e.g., animals and plants) (e.g., bacteria) Larger in size (10 – 100 µm) Smaller in size (0.1 – 5 µm) Copyrights 49  Four Common Cellular Components Prokaryotic cell Which components are present in BOTH prokaryotic and eukaryotic cells? Eukaryotic cell 1 2 3 4 DNA (genetic material) rsscience.com Copyrights 50  Eukaryotic cells contain many organelles Organelles are sub- cellular structures with specialized cellular functions Many organelles are membrane-bound to form a separate compartment within the cytosol for specific compounds and reactions Organelles support complex functions of a eukaryotic cell (e.g., movement, protein synthesis) Lippincott Molecular and Cell Biology Copyrights 51 Eukaryotic Organelles and their Functions 52  Mini-Activity: Build a Eukaryotic Cell http://sepuplhs.org/high/sgi/teachers/cell_sim.html Build a complete animal cell and plant cell (eukaryotic) Hover over each organelle for more details about its function. Copyrights 54  Solution: Animal vs. Plant Cell Copyrights 55  Comparing Animal vs. Plant Cells Lumen Learning Components of an animal (left) and plant (right) cell Copyrights 56  Clicker Question Match the following organelles with their function: a. ribosomes i. Movement b. microtubules ii. Photosynthesis c. mitochondria iii. Protein synthesis d. chloroplasts iv. Digestion e. lysosomes v. Cellular respiration A. a-i, b-ii, c-v, d-iii, e-iv B. a-iii, b-i, c-v, d-ii, e-iv C. a-ii, b-v, c-iii, d-i, e-iv D. a-iii, b-i, c-iv, d-ii, e-v Copyrights 57  Clicker Question Which of the following would be a possible process to study in the bacterium E. coli? 1. how cells decode DNA instructions to make proteins 2. formation of the endoplasmic reticulum 3. trafficking of lysosomes within the cell 4. how mitochondria get distributed to cells during cell division Copyrights 58  Summary: Cell Structure and Organelles Prokaryotic cell: Unicellular organisms (e.g., bacteria cell) without a nucleus or membrane-enclosed organelles Eukaryotic cell: Plant and animal cells with a nucleus and membrane-enclosed organelles Organelles are sub-cellular structures with specialized function All cells have four common components: 1) plasma membrane, 2) cytoplasm, 3) genetic material (DNA), and 4) ribosomes Some cells have specialized structures unique to them – e.g., cilia in human airway cells, flagella in bacteria and sperm cells Plant and animal cells have many fundamental similarities, but also some striking differences – e.g., cell wall and chloroplasts in plants Copyrights 59  Mini-Activity: Visualizing Cells w/ Light Microscope Make your way to the microscopes to view the following three types of cells: Human buccal epithelial Onion root tip cells Human Blood Smear (cheek) cells Carolina Biological Supply Red Blood Cells (RBC) http://www.olympusmicro.com White Blood Cells (WBC) Carolina Biological Supply How do these cells differ from each other? How are they similar? Copyrights 60