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College of Graduate Studies

First Year curriculum courses - Fall 2016

Introduction
An integrated curriculum comprised of three consecutive courses (CGS 765, CGS 766 and CGS 767) and one concurrent course (CGS 768) has been designed to present a foundational study of cell structure and function from biochemical, genetic, molecular and cell biological perspectives. The full curriculum is taken by all first-year PhD students in the biomedical sciences, but individual courses can also be taken by others. The participation of a small number of faculty ensures a cohesive presentation of the material with “foreshadowing” and “retrospective” integration across topics. In addition to lectures, the didactic sessions will include presentation of data from the literature, discussion, and small-group exercises. Hallmarks of the courses are the “THINK” sessions (thoughtful integration of new knowledge), which typically occur on Fridays and are 3 hours in length. THINK sessions enable an in-depth discussion of specific topics which illustrate and integrate concepts developed in the previous sessions. This iteration of underlying principles within the context of a specific biological problem or mechanism help students grasp the importance of fundamental principles to problems that they may research in the future.

 

Quicklist

Proteins: Dynamic Structure and Functions (CGS 765)

Craig Beeson, PhD and Shaun Olsen, PhD, Course Co-directors

Course Description
The 18 sessions of this 5-week, 3 credit hour course present fundamental principles of protein structure and function. Proteins, the most abundant and diverse family of macromolecules within the cell, play a myriad of essential catalytic and structural roles within the cell. They undergo multiple post-translational modifications and interact with numerous partners, including other proteins, RNA, DNA and membranes. These topics will be considered within the context of health and disease, with an emphasis on the molecular mechanisms underlying fundamental cellular processes and underscoring the impact of mutant proteins on cell behavior and the importance of proteins as therapeutic targets.

Course Directors
The course will be co-directed by Drs. Craig Beeson (843-876-5091) and Shaun Olsen 843-876-2308). Dr. Beeson has a long track-record as a professor in the first-year curriculum for CGS PhD and MS students, and his participation in the current course reflects his knowledge base in protein chemistry and his teaching experience in this area. Dr. Olsen is an Assistant Professor whose expertise is in structural biology and enzymology, and he has served on the First Year Task Force that has redesigned the CGS curriculum for this coming year. Thus, these two professors are ideally suited to lead the first module in this curriculum. Continuity within the  course will be facilitated by the fact that the co-directors will be teaching ≥ 12 of the 18 classes.

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Genes: Inheritance and Expression (CGS 766)

Tilman Heise, PhD and David Kurtz, PhD, Course Co-directors

Course Description
The 25 sessions of this 7-week, 4 credit hour course present the fundamental principles of  inheritance, maintenance and expression of the genetic material. The first 6 sessions focus on the principles and practice of classical and molecular genetics, and the next 7 focus on the replication, repair and transmission of the DNA genome within the context of the mammalian mitotic and meiotic cell cycles.     The final 11 sessions focus on the expression of the genome, incorporating discussions of transcription, epigenetic modifications of DNA and histones, nucleolus and rRNA synthesis and maturation, mRNA processing, nuclear export and translation, and regulation by non-coding RNAs.

Course Directors
The course will be co-directed by Drs. Tilman Heise  (843-792-6979) and David Kurtz (843-792-5844). Dr. Heise has a long track-record as a professor in the first-year curriculum for CGS PhD and MS students, and his participation in the current course reflects his knowledge base in RNA biology and the regulation of gene expression and his teaching experience in these areas. Dr. Kurtz has also been a mainstay, and he has served on the First Year Task Force that has redesigned the CGS curriculum for this coming year. Thus, these two professors are ideally suited to lead the first module in this curriculum. Continuity within the course will be facilitated by the fact that the co-directors will be teaching 11 of the 24 classes, which represents the entire second block of the course. Dr. Traktman, the Dean of CGS, has been actively engaged in graduate education for >30 yrs and has significant experience teaching the topics assigned to her in the Molecular Genetics block of this course. Dr. Gangaraju and Dr. Smits are Assistant Professors with expertise in the areas that they will be teaching as well, and Dr. Mohanty has been teaching topics on DNA metabolism for several years.

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Cells: Organization and Communication (CGS 767)

Amy Bradshaw, PhD and Robin Muise-Helmericks, PhD, Course Co-directors

The 18 sessions of this 5-week, 3 credit hour course address the fundamental principles of cell structure, compartmentalization, and function. The first 10 sessions focus on the structure, function and dynamics of the endomembrane systems of the cell, the cytoskeleton, major organelles and programmed cell death. The final 7 sessions address cell:cell and cell:matrix interactions and the complex process of signal transduction. The overarching principles involved in the process of signal transduction, which most often involves the transduction of a signal from an extracellular ligand to a nuclear response, will bring together the principles discussed in the initial part of this course and those discussed in modules I and II.

Course Directors:
The course will be co-directed by Drs. Amy Bradshaw (843-792-4959) and Robin Muise-Helmericks (musehelm@musc.edu, 843-792-4760). Dr. Bradshaw has a track-record as a professor in the first-year curriculum for CGS PhD and MS students, and her participation in the current course reflects her knowledge base in cell:cell and cell:matrix interactions and her teaching experience in these areas. Dr. Muise-Helmericks has also been an engaged teacher, has an active research program in cell biology and has served on the First Year Task Force that has redesigned the CGS curriculum for this coming year. Thus, these two professors are ideally suited to lead the third module in this curriculum. Continuity within the course will be facilitated by the fact that the co- directors will be teaching 8 of the 18 classes in this course. Dr. Gemmill also has significant experience as a cell biologist and a teacher in the CGS curriculum. Drs. Olsen and Kurtz have served as members of the First Year Task Force, and along with Dr. Muise-Helmericks will facilitate integration of this course with the first two modules of the curriculum.

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Further Course Details

Course hours, contact hours, and credit assignment
Each of the three courses will meet for 9 hours per week, spread among 4 days; the class will meet  for 2 hours on 3 of those days and for 3 hours on one day, typically Friday. The class will meet from 9:00 am -11:00 am or 9:00 am -12:00 pm.

Format and texts
Attendance at all classes is required of all students. The didactic sessions in these core course will include lecture, discussion, presentation of data from the literature, and group exercises. For example, students may be asked to work on problems, or to utilize internet-based or software-based searches for protein motifs or domains. They may be asked to break into small groups for problem-solving sessions. Active engagement of the students will be important, although much of the foundational material will be presented in lecture format.

The THINK sessions will bring a new topic of discussion into the class and will serve to illustrate and integrate the principles that have been presented in the more general lectures. These sessions (3 hours in length) will be particularly suited to discussion and problem solving.

The assigned textbook for the three consecutive courses of the Fall curriculum is the 6th edition of “Molecular Biology of the Cell”, edited by Alberts et al. Incoming students will have been given introductory chapters to learn and/or review over the summer prior to joining to MUSC. During the courses, students will be assigned reading and/or problems from the book. Additional reading materials in other textbooks or review articles may be assigned as deemed appropriate, and materials from the scientific literature may also be used in class.

Evaluation
Exams
Performance on closed-book, in-class examinations will determine whether students have learned the fundamental quantitative and qualitative material presented in the class, and will also prompt students to think about how the fundamental principles that they have learned can be applied to current topics of biomedical inquiry. Course directors and instructors will outline the key objectives to students as the classes progress. The examinations will be designed to integrate material from different class sessions to minimize compartmentalized learning and maximize "bigger picture" thinking. Questions will be of the long-answer format, and may require students to solve problems, and design experiments or propose models. Students will have the opportunity to complement their written responses with drawn models and figures in an effort to develop their skills in using visual aids to more effectively convey complex concepts.

Participation
Student participation will also be evaluated, and will reflect attendance, participation in discussions and exercises, and in particular participation in the “THINK” sessions. Each professor will be given a student roster and asked to grade student participation as “needs improvement”, “competent”, or “exemplary”.

Grading
Participation: Overall and during the THINK sessions. Overall: Faculty will evaluate the attendance, preparation, and participation in the overall discussion and any group exercises that occur. THINK sessions: Here, participation will be more structured and evaluation will be based on how the students have prepared for, and participate in, the discussion of the prescribed material and contribution to small group and individual activities. The following rubrics will be used to evaluate participation and performance on examinations:

Participation Rubric

CriterionNeeds improvementCompetentExemplary
Active participationDoes not contributeResponds to direct queries, sometimes volunteersOften volunteers, initiates new discussions on topics related to class topic
Relevance of participation to topic under considerationContributions are sometimes off-topic or distractingContributions are always relevant to discussionContributions are relevant and promote in- depth or novel analysis
Evidence of level of preparationDoes not appear to have read the material in advance and/or has little comprehensionComes prepared to class and can take advantage of opportunities for discussionComes prepared and may bring additional material into discussion beyond what was assigned
Listening/ cooperationInattentive, doesn’t respect or contribute to teamParticipates regularly, responds well and contributes to teamParticipates well and shows leadership: promotes active participation by others

Examination Rubric

 ExemplaryCompetentNeeds Improvement
Clarity / OrganizationResponses are well thought out and organized, utilize proper grammar, connections are clear and transitions are smoothResponses are adequate and are reasonably well organized, connections are generally clear and most transitions are smoothResponses are incomplete or use poor grammar and punctuation, are disorganized, connections are not clear and/or transitions are not smooth
ComprehensionProvide logical responses beyond what is presented in class, integrates literature and class material, and exhibits independent thinking

Provide responses that merely repeat facts with no integration of concepts and/or exhibits minor flaws in logic

Provide responses that only repeat class material and/or are fatally flawed in terms of logic

Final grades will reflect overall student participation (10%), participation in the THINK sessions (10%) and the examination (80%).

The course will utilize the E*value system to obtain student feedback and faculty evaluation.
 

Techniques and Experimental Design (TED) (CGS 768)

Dr. Jennifer Isaacs, Course Director
Cell and Molecular Pharmacology Hollings Cancer Center, HO702E 843-792-8393

Course Description
CGS 768 is the fourth constituent course of the Fall semester and runs concurrently with the other three courses (CGS 765, CGS 766 and CGS 767). The course highlights essential tools and approaches required to achieve a high level of competency in biomedical research. Students will be exposed to the practical ‘nuts and bolts’ of a wide variety of molecular biology approaches spanning established basics, as well as timely new techniques. Course material will complement and align with scientific concepts covered in the other three courses. Students will be equipped with the knowledge necessary to tackle basic protein biochemical studies such as protein isolation, understand the basics of genetics, including the use of various gene editing strategies and execution of genetic screens, and be exposed to central concepts and approaches relevant to cell biology. Collectively, this training is expected to provide students with foundational knowledge and an invaluable toolkit that will collectively prepare students to successfully embark on their thesis research.

Course Objectives
The overall objective of this course is to equip students with the practical knowledge necessary to achieve a basic competency in molecular and cell biological techniques. This knowledge will allow students to consider multiple experimental paradigms as they formulate a cohesive experimental strategy relevant to their thesis proposal. The material within TED is expected to further provide a practical foundation and to further reinforce the key concepts presented in the other three Fall courses.

Students will:

- Gain an appreciation for the step-wise and iterative process of scientific inquiry and experimental design.
- Understand the importance of rigorous experimental setup, with inclusion of multiple controls and appropriate replicates.
- Possess the essential tools required to tackle a broad array of scientific questions within the realm of molecular biology.
- Be exposed to publication-quality data that reflects measureable metrics of covered approaches.
- Understand the limitations and strengths of complementary methodologies.
- Understand appropriate interpretations of relevant data, and how to design logical subsequent experimental steps.
- Be able to describe basic biochemical approaches to isolate proteins, protein complexes, identify post-translational modifications of respective proteins, and to assess protein activity.
- Understand the complex interplay between proteins and DNA or RNA, and how to evaluate the genome-wide distribution of protein interactions with DNA and RNA.
- Gain an understanding of cloning basics including gene editing, and use of relevant tools to perform genetic screens, and use of associated phenotypic and cellular assays
- Understand approaches to measure both static and dynamic gene transcription, and the respective roles of RNA processing and epigenetic pathways as modulators of this process
- Understand approaches to measure DNA repair and replication, and relevancy to maintenance of the cell cycle, proliferation, and cell survival.
- Understand the basics of microscopy, and ability to visualize protein-protein interactions, identify organelles, utility of super-resolution approaches, and techniques to evaluate dynamic protein movement, as well as define ultra-structural cellular components.
- Understand the integrative components that regulate cellular architecture, and how these cooperate to influence cell motility and organization into 3-dimensional structures.

Time/Location
Wednesday 9:00 am -11:00 am
Course meets Wednesday August 24 - Wednesday December 14 Location to be determined

Grading:
25% of the final grade will be based upon student participation. In addition to a didactic lecture component, the lectures will consist of interactive discussions whereby students will be encouraged to discuss conceptual aspects of experimental design and applicable components thereof. The remaining 75% of the merit grade will be determined by student performance on 3 exams, with each exam comprising 25% of the overall grade. Each exam will be a take home format wherein students have 1 week to complete the assignment. Exams will consist of a defined and interconnected set of hypothetical research questions that the student is asked to resolve via a rationally selected experimental approach or suite of approaches, drawn from the lecture material from the corresponding block. The objective of the exam is to evaluate whether the student has appropriately integrated the material within a conceptual and analytical framework. The Course Director will ensure that the instructor-designed questions facilitate conceptual integration and reflect this philosophy.

Course Strength
TED represents a unique and timely approach to learning. The topics covered in TED are highly complementary to the foundational concepts addressed in the other three Fall courses. A major tenet of the Biomolecular, Genetic and Cellular Essentials Fall coursework is to integrate knowledge, as evidenced by the Friday ‘THINK’ sessions. Building upon this framework, TED will reinforce student understanding of the core material, and will similarly integrate knowledge through lectures, discussions, and thought-provoking exams. A central goal of TED is to impart students with the practical experimental knowledge needed to embark on the process of scientific inquiry. Student exposure to the conceptual knowledge in the core courses, in tandem with the highly complementary experimental framework covered in TED, represents an optimized training paradigm.

Recommended Materials:

Molecular Biology of the Cell, 6th Edition (2014), Bruce Alberts et al. http://www.jove.com/science-education-database/2/basic-methods-in-cellular-and-molecular- biology
http://www.jove.com/video/51897/recombinant-protein-expression-for-structural-biology-hek- 293f
http://www.jove.com/science-education/5074/molecular-cloning

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Lecture 1
8-24

Paula Traktman 

Experimental design basics-1st 45 minutes

The basics of protein isolation
Chromatography (ammonium sulfate cut, ion exchange, gel filtration, affinity)
Differential centrifugation-prepurification
Gel electrophoresis (SDS PAGE, IEF, 2-D, immunoblot)

Lecture 2
8-31

Stuart Parham
Shaun Olsen

Identification of Protein Structure

NMR
X-Ray Crystallography
Circular Dichroism
- Use of CD and NMR to assess protein stability and flexibility
Cryo EM for protein and complex structure

Lecture 3
9-7

Lauren Ball

Evaluation of Protein Interactions, Modifications, and Domains

Immuoprecipitation (endogenous or tagged proteins)
Mass Spectrometry – proteins complexes, PTMs, quantitation and stoichiometry
Blast searches – homology and protein domains SPR  and Proximity assays
Challenges – detection limits, known spectra, reproducibility, etc
Lecture 4
9-14

Je-Hyun Yoon

Mapping Protein-nucleic acid Interactions

Genome-wide mapping of DNase-sensitivity
Target-specific mapping of Transcription factor binding sites on chromatin Transcriptome-wide mapping of protein-RNA interaction
In vitro analysis of protein-nucleic acid interactions (biotinylation, EMSA)

Lecture 5
9-21

Patrick Nasarre

Assessment of Protein Function

TGFD-ERK signaling
Assessment of signal transduction
Kinase assays to evaluate activity of intermediates Specific activities/linear range, detection strategies
ExamTake Home Exam Proteins Section

Lecture 6
9-28

Hiu Wing Cheung

Genetic Screens and DNA Detection

Screens/selections – Bacteria, yeast culture Yeast 2-hybrid
Karyotyping, Chromosome painting, FISH Haploid screens

Lecture 7
10-5

Dave Turner

Genetics – Cloning Basics
Cloning Vectors, restriction enzymes ligases, etc. PCR in cloning
Cellular delivery - Lentiviral vectors, Adenoviral Vectors Gene silencing/overexpression
DNA detection - Southerns
Lecture 8
10-12

Bart Smits

Reverse Genetics
Genomic and cDNA libraries
Phenotypic effects of genetic sequences
Gene editing and silencing as tools to assay phenotype
Lecture 9
10-19

Rick Visconti

Evaluation of Cell Cycle and DNA replication
DNA Replication Assays
Detection of DNA damage, H2AX, etc Detection of proliferation and apoptosis Assessment of cell cycle
Lecture 10
10-26

Jamie Barth

Assessing Specific and Global Transcription
RNA seq and Microarray Promoter Assays
qPCR and target validation
Analysis of DNA methylation and Histone marks
Discuss measurements of steady state (static) vs kinetic transcription Introduction of Encode project
Lecture 11
11-2

Tilman Heise

RNA-based Regulatory Mechanisms
mRNA splicing and polyadenylation
Monitoring mRNA localization, trafficking, and stability microRNA processing and activity
EXAM

Take Home Exam Genetics and Transcription

Lecture 12
11-9

Paul McDermott

Approaches to Monitoring Protein Translation
Polysome loading (Preferential transcript translation) Cyclohexamide ,35S-met labeling, non-radioactive methods (SunSet) Cell free systems and in vitro translation
Lecture 13
11-16

Amy Bradshaw

Cell Architecture and Cell Motility
Cell shape- microscopy and Image J ratios
Microscopy and visualization of actin, cytoskeleton, nuclear membrane Cellular requirements for cell motility
Cell motility assays
11-23Thanksgiving
Lecture 14
11-30

John Lemasters

Organelle Visualization Organelle specific dyes Electron miscroscopy
Light microscopy, fluorescence, confocal FRAP, FRET
Super-resolution
Co-localization, Proximity ligation assays
Lecture 15
12-7

Muise-Helmericks Kelly Argraves

Cells to Tissues
ECM specificity - adherence to differential matrices (laminin, fibronectin) Barrier function -  Fluorescent dyes or Electrical impedance
Microscopy and visual analysis of junctions
3D/organoid growth of cells – oxygen and nutrient gradients = complexity
Lecture 16
12-14

Joe Blumer

G-Proteins as a Vignette of Signaling and Pharmacologic Targeting
Assessment of signal activation, effectors
Use of pathway inhibitors to delineate specific pathways Respective pharmacology and challenges
EXAMTake Home Exam Cell Biology

 

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