Download Advanced Molecular and Cell Biology (Dorn, Holton)

BIO. 372/572 ADVANCED MOLECULAR AND CELL BIOLOGY (3 cr)
LECTURER: Drs. Lisa Dorn and Bea Holton
Spring 2007
OFFICE: LD: HS45, BH: HS42, 142
PHONE: LD: 3064, BH: 7087, 1102
E-MAIL: [email protected]; [email protected].
OFFICE HOURS:
LD:. Mon 1:50pm to 3:50pm, Thurs 1:50 to 3:50pm
BH: M 3:00-4:00pm, Th 9:40-11:40, or by appointment. I usually arrive on campus between 8 am and
4:00pm.
LECTURE HOURS: 11:30am-12:30pm MWF in Halsey Science HS457.
TEXT: Lodish, et. al. (2003) Molecular Cell Biology, 5th edition, W.H. Freeman and Company,
OBJECTIVES:
Molecular and cell biology concerns the anatomy, physiology and biochemistry of animal and plant cells.
This course will be theme-based, meaning that we will cover about 5-6 topics of current interest to cell and
molecular biologists. We will use these topics to learn about general processes such as receptor/ligand
interactions, signal transduction, cytoskeleton (and control of its distribution), gene regulation, cell cycle and
protein translocation. For the sections on molecular biology, we will cover topics concerned with the
molecular mechanisms that generate variation at the phenotypic level and the consequences for the evolution
of that phenotype. Throughout this course, we will read and discuss original papers from the literature so
that students will also become familiar with the methods and the logic that scientists use to test their
hypotheses.
Due Dates and Exam Dates
Date
Significant events
Instructor
12 Feb
First paper discussion
Dorn
12 Feb
Writing Assignment Handout#1
Dorn
14-Feb
Discuss handout #1
Dorn
21 Feb
Second paper discussion
Dorn
26 Feb
Hand in 1st writing assignment
Dorn
2 March
EXAM 1
Dorn
16 March
Switch instructors
Holton
EXAM 2 Writing Assignment #2 Handout
Holton/Dorn
20 April
Writing Assignment #2 Due
Holton
20 April
Writing Assignment #3 Handout
Holton
4 May
Hand in 3rd writing assignment
Holton
9 May
EXAM 3
Holton
4 Apr
Dates for paper discussions will be subject to minor changes. Each
Outline of Lecture Topics*
THE MOLECULAR BIOLOGY HALF:
In this half of the semester we will begin by reviewing DNA and chromosomal structure before moving on to
the mechanisms cells use to regulate gene expression. This topic of regulating gene expression is perhaps
the most rapidly advancing and fascinating fields of genetics research today. In large part that rapid advance
is the direct result of the technological advances that have become possible in the “post-genomics” era, like
surveying the expression of every single gene in an organism’s genome (20,000 human genes, 24,000 plant
genes) by studying an array of fluorescent dots on a microscope slide. Many questions that had not even
been thought of were suddenly raised when it became possible to test them. The list ranges from determining
which of the ~20,000 human genes are expressed in diseased and normal tissues to looking for the key genes
that have driven evolution. Besides the breakthroughs that arose via genomics, recent accidental discoveries
have uncovered totally unexpected mechanisms of regulation. By the end of this section you will be familiar
with these mechanisms of gene regulation, you will learn about the newest and oldest techniques of studying
gene expression and we will discuss the implications of gene expression to evolution and human disease.
Molecular structure of genes & chromosomes – Gene expression is indirectly driven by the structure of
chromosomes and the distribution of regulatory elements in the sequence of nucleotides. Here we will
briefly review how sequences of nucleotides are arranged in semi-discrete regions (depending on who is
arguing) of the chromosomes to encode the information in a gene that will be expressed.
Ch. 10
Parts of Chapter 9
(I will refer back to chapter 9 several times in the semester to review experimental techniques)
Transcriptional Regulation -- Most gene expression is regulated at the level of production of mRNA. Here
we will study the various mechanisms by which that is accomplished. Here we will begin our discussion of
the techniques that have evolved out of genomics and their implications for investigating disease.
Ch. 11
Post-Transcriptional Regulation -- This is where we will study epigenetic molecular mechanisms of gene
expression: such as hypermethylation, RNA interference and other mechanisms of post-translational gene
silencing.
Ch. 12
Molecular evolution -- Here we will try to bring together what we know about gene expression to the
study of how DNA sequences inside and outside of the gene regions of a chromosome have evolved and to
some extent the influence of gene expression on speciation and phenotypic evolution.
The literature
CELL BIOLOGY HALF:
Protein Structure and Function – Proteins drive nearly all cellular chemical reactions and cellular
activities. They do this by changing their shape and therefore their interactions with other molecules. To
truly understand how cells function, one must appreciate how protein shape is controlled. We will briefly
review protein structure and activity.
Ch. 3
Chemotaxis – Many cells, from macrophages to Dictyostelium (a slime mold) to migratory embryonic cells,
must sense concentration gradients and migrate up those gradients. How do cells sense gradients in their
environment? How do cells respond to those gradients so that they can move in an oriented fashion? How
do cells use environmental signals to control the organization of their cytoskeleton? To answer these
questions, we must consider
How cells receive signals
Ch. 13
How cells transduce signals so that cell behavior and gene expression
alter
Ch. 14
How cells integrate signals and gene controls
Ch. 15
How cellular cytoskeleton is formed and integrated with cellular signaling
Ch. 19, 20
Memory – Long term potentiation is the process by which neurons “store” information that allows for
memory. What is the cellular/molecular basis of memory? To answer this question, we must consider
How cells control ion flow and small molecule flow across the cell membrane
Ch. 7
How cells change the elaboration of membrane/protein structures such as synapses and
how they control receptor number and density
Ch 16, 17
How memory might be perpetuated
(no text ref.)
Mystery topic to be announced.
*This is an advanced class that covers current, interesting topics. If you have topics that YOU would
like to see covered, please give them to us and we will try to work them in.
GRADING: 40% of the grade will be based on three in-class short essay exams (each exam will include
some comprehensive questions), 45% on three short, research-style papers, and 10% will be based on one
oral presentation, 5% participation in paper discussions (student must be prepared to discuss figures from
discussion papers). 92-100% = A, 89-91 = AB, 82-88 = B, 79-81 = BC, 72-78 = C, 68-71 = CD, 60-67 = D,
below 60% = F. Grades will only be “curved”, if necessary and not until the final total has been calculated.
ORAL PRESENTATION: Undergraduate students will work in pairs; graduate students will work as
individuals. Undergraduates will report, in 20 min., the results of one research paper from the literature.
You may choose any topic that interests you as long as it is relevant to cell or molecular biology, and as long
as the paper comes from a journal that reports primary research (do not use Scientific American, Discovery,
Trends in Cell Biology, etc.). Much of your talk will involve explaining the data to the audience so that the
audience can determine the validity of the work. Graduate students must report on 3 papers and may take up
to 25 min.
GRADUATE STUDENTS: Graduate students will be graded by a higher standard than undergraduates.
Graduate students are expected to be proficient in writing. At this point, they should have a good command
of scientific vocabulary and use it appropriately. They should understand commonly used scientific
techniques and knowledgeably discuss data gleaned from such methods. Their data interpretations should
show insight into the larger, more general problems being addressed. Additional assignments: 1) As
mentioned above, graduate students must give an oral presentation by themselves; and 2) they must prepare a
short (2pg) mini-review of the literature surrounding the topic of the presentation (due at the time of the
presentation).
WRITING ASSIGNMENTS:
General Instructions
We will provide students with selected data from the literature that are relevant to theories discussed in class.
Students are to treat the data as though they were their own and as though they wanted to present them to
others in their field. Consequently, you must first capture the interest of the reader by explaining the
significance of the hypothesis tested in your paper; second, explain clearly the results so that the reader
understands their meaning and draws the same conclusions as you and, finally, discuss how your results
expand upon knowledge published to date. Each paper will have:
- Introduction that gives some background information but mostly outlines questions in the field
(that will be addressed by your data) and significance of the work presented. A rationale statement is often
useful.
- Results section that explains the data. What do the data show? (To answer this question, you may
also have to explain a bit about the techniques used and the rationale for doing specific experiments.) Why
were certain controls done?
- Discussion section in which a reasonable hypothesis is formulated from the data.
This sounds like a lot of writing, but, in fact, the maximum page length will be two typewritten, singlespaced page (font no less than 12). The key is to think clearly, write concisely and say exactly what you
mean…no more, no less.
Students may discuss the data (and interpretations of the data) among themselves. However, and they can
ask us questions, preferably in class where all can profit from the questions and answers.