Graphic representation of membrane with ion channels Welcome to the Membrane Transport (SC/BIOL 4151.03) (crosslisted as SC/BCHM 4141.03) course website! Announcements and most course information will be posted here, so please check for updates often.

19 may 2015: Membrane Transport will be taught by Jean-Paul Paluzzi in 2015/2016, probably with a Moodle course website. Source material on this website may still be useful to students.

The course description includes past syllabi, course evaluations, and sample tests and assignments that should be helpful to prospective enrollees.

Please be aware that the study of membrane transport is intrinsically mathematical in nature. The mathematics is crucial for understanding energetics and kinetics of transport mechanisms. The term tests and assignments should give you an idea of the mathematical nature of the course.

Announcements

6 jan 2015: Thank you all for making this such an enjoyable course, and best wishes on all your future transporting endeavours!

Course Description (fall, 2014)

BLM technique and ion channel activity The fundamental properties of solute transport are presentedby discussing active ion pumps, passive transporters and ion channels of bacteria, plants and animals. The role of transport in regulating the intracellular environment in animals and plants is emphasized. Three lecture hours. One term. Three credits.

Cross-listed to: SC/BCHM 4141 3.0. Prerequisites: SC/BIOL 2020 4.0; SC/BIOL 2021 4.0; SC/BIOL 3010 3.0 and SC/BIOL 3110 3.0 strongly recommended as prerequisites or corequisites.

Course Director:

~~Roger Lew, 229 Farquharson Building (please feel free to drop by my lab if you need to speak with me). Phone: (416) 736-2100 ext 66114. Email: planters@yorku.ca~~

Schedule:

Lectures (Location: LSB [Life Sciences Building] 101) are on Tuesday and Thursday (8:30 to 10:00 AM).

Textbook:

Berg, H.C., Random Walks in Biology. Princeton University Press.

Berg presents the physical basis of random walks: the movements of molecules. Random walks are the foundation of diffusive fluxes, and are the starting point for a rigorous exploration of molecular transport at membranes. The presentation is physics-oriented.

Byrne, J.H. and S.G. Schultz. Membrane Transport. An Introduction to Membrane Transport and Bioelectricity. (Course Kit)

Byrne and Schultz are writing for a medical student audience. So, the presentation is not very rigorous. It is a gentler introduction to all aspects of transport, including action potentials. It should be helpful to students as an overview.

Assignments and Grading:

Below is the assignments and grading scheme decided by students in 2014 (here are compiled examples of grading and assignment schemes [png] decided by students).

Take Home Assignments (highest scoring 15%, middle scoring 10%, lowest scoring 5%) (30% total)

Two term tests and the final exam (highest scoring 40%, middle scoring 20%, lowest scoring 10%) (70% total)
(Term Test Dates 16 October, and 18 November)

In the event of a documented absence from a term test, the weight (10%) will be transferred to the final exam

Other Information:

The mechanisms of transport, the biochemical properties of the transporters and their primary structure are very similar in higher plants and fungi, bacteria and animals. So, examples of well-studied transporters will be drawn from all kingdoms. Some possible topics: arsenic transporters, various active pumps, water channels, light-gated and various other ion channels. Please be aware that the study of membrane transport is intrinsically mathematical in nature. The mathematics is crucial for understanding the energetics and kinetics of transport mechanisms. Regulation of the intracellular environment, the a priori role of cellular transport, will be emphasized. Here is the formal course information outline [pdf] (with learning objectives).

Osmotic responses of fungal hpyha

Past Syllabi:: 2014 Syllabus [pdf]; 2012 Syllabus [pdf]; 2010 Syllabus [pdf]; 2007 Syllabus [pdf]; 2005 Syllabus [pdf]

Past Course Evaluations (student comments about the course -slightly edited- are included):: 2014 Evaluation [pdf] (with advice to prospective students); 2012 Evaluation [pdf] (with advice to prospective students); 2010 Evaluation [pdf] (with advice to prospective students); 2007 Evaluation [pdf]; 2005 Evaluation [pdf]; 2004 Evaluation [pdf]

Past Assignments and Tests

Fall, 2014: tests and assignments with key [pdf]
Fall, 2012: tests and assignments with key [pdf]
Fall, 2010: tests and assignments with key [pdf]
Fall, 2007: tests and assignments with key [pdf]
Fall, 2005: term tests [pdf]

Sample Assignments (presented as is)

With answers: permeability ratio analysis [pdf]; capacitance analysis [png]; energetics analysis [png]
The examples below are provided without answers: cell flux [png]; diffusion potentials [png]; Goldman transport [png]; transporter number [png]

Miscellanea

5 oct 2012: Transport in the News A new painkiller from venomous snakes?

We don't see much (if any) Transport in the News, but this one caught my eye, and was covered by many mainstream media outlets. It's the discovery of an analgesic in the venom of mamba snakes. The 'toxin' is a long (57 aa) polypeptide with many cysteines (disulphide bridges create a well-defined three dimensional structure). It specifically inhibits acid-sensing ion channels which are part of pain pathways in humans (and other animals). The sciency article is in Nature. BBC is one of many media outlets who picked up the story.

Phospholipid isolations: Lipid extractions (including phospholipids) rely upon a strategy of solvating lipids, to separate them from the many other constituents of the cell (proteins and carbohydrate for the most part). Of these three major groups, lipids are by far the most hydrophobic, and can usually be solvated by hydrophobic solvents. The ones used most commonly are chloroform and methanol. The typical ratio (by volume) is 2 parts chloroform to 1 part methanol. Once the tissue has been homogenized (usually with a glass homogenizer [jpg]), the homogenate separates into two phases: the lower phase consists mostly of chloroform and is where the hydrophobic lipids are found. At low concentrations, chloroform is a 'narcoleptic', that historically was used as an anesthetic. It has a 'sweet', very characteristic odour. The mode of anesthetic action remains controversial: but its efficacy depends upon its intercalation into biological membranes, disrupting normal transport activity. Most biophysicists believe that inhibition of Na+ channels is a key element of its anesthetic action. Chloroform is toxic (very much so!) at relatively low concentrations. Rapid entry into the body is via the lungs, but it can even penetrate through skin, and latex gloves!). Caution is advised.... In ancient times, we would assure ventilation by opening a window. Now, a fume hood is obligatory.

Web Resources

TransportDB: Genomic Comparisons of Membrane Transport Systems.
Qinghu Ren, Katherine H. Kang, and Ian T. Paulsen (2004) TransportDB: A relational database of cellular membrane transport systems.
Transporter Classification Database
A classification of many if not all transport systems in a variety of species from Milton Saier's Laboratory, and other links.
P-type ATPase Database from Kristian B. Axelsen
A compilation of ion pump enzyme phylogenies, classification, and references.

Readings

Below are supplemental readings in support of lectures over the term

Course Notes [pdf] These course notes focus on the mathematical underpinnings of transport presented in lecture. They are not lecture notes, but may serve as a useful study aid for students.	Fluidity [link] A Trends in Biochemical Sciences paper (1986) by Anthony Carruthers and Donald L. Melchiorin, it gives a helpful overview of how membrane fluidity affects membrane protein activity.
Membrane Protein Structure [ResearchGate] Suzanne Scarlata wrote this brief overview of membrane structure for a 'Biophysics Textbook Online', once provided as an educational resource by the Biophysics Society, but now available from ResearchGate.	Pressure: NaK-ATPase [link] It's not easy to distinguish between temperature and fluidity effects on membrane transport activity. Parkson et al. (1985) used pressure to affect fluidity --separate from temperature-- using the well-known Na,K-ATPase.
Gramicidin [link] The gramicidin channel is a wonderful case study with which to explore channel mediated ion transport across membranes. Wallace (2000) reviews its structure, compared to other ion channels.	Arsenic Review [link] The mechanisms of arsenic transport reveal the evolution of active transport over the past three to four billion years. Barry Rosen gives a more recent snapshot of arsenic transport, in all its diversity.
Diffusive/Advective Transport [link] Advective flow can deliver nutrients to the membrane. Multicellular colonies of Volvox were used as a model to explore the relative contributions of mass flow (advective transport) and diffusion.	Chemoreception Physics [link] The physics of delivering nutrients (or other substances) to the membrane is explored by Howard C. Berg and Nobel Laureate Edward M. Purcell. These foundational concepts are even germane to delivery of a substrate to the active site of an enzyme.

Mathematics the lighter side


Expanding terms	The value of Pi	Trig and the Matrix

Life or Death	Math Hierarchy	Creative Arithmetic
The Life or Death Solution (courtesy of Scott McClure)

Archived Announcements

2014

15 dec 2014: Here are the scores for the third assignment: [png]

4 dec 2014: Per student request, here is an example showing calculations of electrochemical gradients in cotransport systems (from Cramer & Knapf (1991) Energy Transduction in Biological Membranes): [png]

20 nov 2014: Here is the third assignment in pdf format [pdf]

The assignment is due on Friday 5 December before 4:30 PM. It can be dropped off at room 229 Farquharson Building

13 nov 2014: Location of the Second Term Test: To provide additional space (to spread out), the second term test will be held in:

LSB 105 at the usual lecture time (Tuesday 18 November 8:30AM to 9:50 AM)

Here is a draft of the equations and constants that will be provided to you for the second term test [pdf] (they are unlikely to change).

21 nov 2014: Here is the answer key

6 nov 2014: Here are the lecture notes on pressure-volume relations [pdf]

4 nov 2014: Hints for the second assignment

Finding concentrations of ATP, ADP and Pi can be a challenge. I found values for red blood cells and microbes. One example: Adenylate nucleotide levels and energy charge in Arthrobacter crystallopoietes during growth and starvation. Arch. Microbiol. 122, 69-76 (1979). Another example: Adenine nucleotide levels in Neurospora, as influenced by conditions of growth and by metabolic inhibitors. J. Bacteriol. 114:752-766 (1973). There are others. A last resort (citing my memory) is ATP (0.0025 mol/l), ADP (0.0005 mol/l) and Pi (0.0005 mol/liter).

One resource that you may find helpful for assessing toxic levels of cadmium and mercury is the INCHEM database (use the chemical identity search box).

28 oct 2014: Here is the second assignment in pdf format [pdf]

The assignment is due on Thursday 6 November before 4:30 PM. It can be dropped off at room 229 Farquharson Building

14 oct 2014: Location of the First Term Test: To provide additional space (to spread out), the first term test will be held in:

LSB 105 at the usual lecture time (Thursday 16 October 8:30AM to 9:50 AM)

22 oct 2014: Here is the answer key

2 oct 2014: Here is the first assignment in pdf format [pdf]

The assignment is due on Friday 10 October before 5:00 PM. It can be dropped off at room 229 Farquharson Building

14 oct 2014: Here is the answer key

21 sep 2014: Transport in the News Arsenic in the microbiome

Becase we will be exploring arsenic transport mechanisms (usually to exclude it from the cell, thereby avoiding death), I thought some recent science news or arsenic in food crops from the NY Times might be of interest: Fighting Poisons With Bacteria. In food crops, arsenic accumulation is a bad thing. In rice, one way to minimize arsenic accumulation by the plant is to take advantage of the natural microbial populations that occur around plant roots. It is unlikely that this involves arsenic transport by the bacteria. But still, it shows how topical arsenic in the envrionment is.

14 sep 2014: If you are interested, the Miscellanea section describes lipid isolation using strong solvents like chloroform. It includes a link to the INCHEM database on toxic/hazardous substance in the workplace (including research labs).

Even today, the anesthetic mode of action of chloroform is not well understood, though dissolving your membranes is a clear reason for your cells to die at higher chloroform concentrations.

22 aug 2014: Both of the textbooks are available in the York Bookstore.

Berg (Random Walks in Biology) presents the physical basis of random walks: the movements of molecules. Random walks are the foundation of diffusive fluxes, and are the starting point for a rigorous exploration of molecular transport at membranes. The presentation is physics-oriented.

Byrne and Schultz (An Introduction to Membrane Transport and Bioelectricity --course kit) are writing for a medical student audience. So, the presentation is not very rigorous. It is a gentler introduction to all aspects of transport, including action potentials. It should be helpful to students as an overview. It was reviewed in the journal Brain [png].

4 apr 2014: I have been asked by the University to remind students of the University Senate Policy regarding Academic Honesty: Both the University Policy and additional resources for students.

2012

8 dec 2012: Thank you all for making this such an enjoyable course, and best wishes on all your future transporting endeavours!

4 dec 2012: Final Exam Update

So far, the final exam is a choice of two out of three questions (this may change). Here are the equations and constants [pdf] that will be provided for you.

Date time and place: Saturday 8 December, 14:00 -- 17:00, Chemistry Building Room 115. See you there!

22 nov 2012: Here is your third assignment [pdf](due 3 December by 5:30 PM in Room 229 Farquharson)

Question: Please explain Diffusion to Capture and the role of advective flow so that even your professor will understand it. That is, the explanation should be at a level that is understandable to a second year science student. Your explanation should be grounded in the seminal paper by Berg and Purcell (1977) (Physics of chemoreception Biophysical Journal 20:193-219) and Chapters 2 and 3 in Berg (1993) Random Walks in Biology (pp. 25-47) [library reserves.]

Ground Rules: I expect students to work independently on this assignment. So, please ensure that the work you hand in is your own. You will need to select just a few ideas that you think are important (explaining why you think so). Excessive length is not encouraged. I think that 4 to 6 pages are sufficient. Handwritten is preferred to typewritten, because hand-drawn diagrams will be helpful. I am especially interested in your ability to make the ideas understandable. Stating 'the fluxes are described by this equation' is not helpful, unless you explain what the equation means or what it implies. Finally, clarity of explanation will be very important in grading of the assignments.

22 nov 2012: Here is a link to optogenetics in action from Nature [youtube]. It's a good overview of the 2010 Method of the Year.

17 nov 2012: Final Exam: Date, Time and Place.

Saturday 8 December, 14:00 -- 17:00, Chemistry Building Room 115

17 nov 2012: Don't forget the term test on Tuesday!

So far, the test is a "select only one of the following two questions". Equations, constants and other information will be provided, here they are so you can preview them [pdf].

31 oct 2012: Here is the second assignment [pdf].

The assignment is due on Friday 9 November before 4:30 PM. It can be dropped off at room 229 Farquharson Building

Here are my lecture notes for Arsenic Energetics [pdf] from Tuesday's lecture.

1 nov 2012 update: For concentrations of ATP, ADP and Pi, you should be able to find realistic values by searching on adenylate energy charge (this is used to measure the energy status of a cell, most articles will provide concentrations of ATP, ADP and Pi).

6 nov 2012 update: Finding concentrations of ATP, ADP and Pi appears to be a challenge. I found values for red blood cells and microbes. One example: Adenylate nucleotide levels and energy charge in Arthrobacter crystallopoietes during growth and starvation. Arch. Microbiol. 122, 69-76 (1979). Another example: Adenine nucleotide levels in Neurospora, as influenced by conditions of growth and by metabolic inhibitors. J. Bacteriol. 114:752-766 (1973). There are others. A last resort (citing my memory) is ATP (0.0025 mol/l), ADP (0.0005 mol/l) and Pi (0.0005 mol/liter).

26 oct 2012: Case Study Suggestions?

I checked on some of the suggestions from last lecture (toxin, secondary metabolite transport and neurons), thinking that opioid transport would work --from biotech efforts to synthesizing them in culture to their transport and mechanisms of action in mammalian CNS-- but came up empty (surprisingly little has been done on their transport). Are there other suggestions? Thanks! Roger

15 oct 2012: Don't forget the term test on Thursday!

I haven't finished writng the test yet. So far, it is a "select only one of the following two questions". Equations and constants will be provided, here they are so you can preview them [pdf].

12 oct 2012: The Gramicidin Case Study lecture notes are available.

I have mounted them on the Moodle website.

9 oct 2012: Gairdner Lecture Circadian rhythms: Molecules, neurons and circuits.

The Gairdner Awards are given to some of the best scientists in the world (some Gairdner awardees eventually go on to win the Nobel Prize). Dr. Michael Rosbash is one of the 2012 Canada Gairdner Laureates, and York is honored to have him give a lecture on Wednesday 24 October in the Senate Chamber (N940 Ross Building) at 1:30pm. It's a wonderful opportunity to hear from an eminent scientist, I hope you are able to attend.

2 oct 2012: Here is the first assignment in pdf format [pdf]

The assignment is due on Friday 12 October before 4:30 PM. It can be dropped off at room 229 Farquharson Building

2 oct 2012: The Movement of Molecules Through Membranes lecture notes are available.

I have mounted them on the Moodle website.

Update: For those of you interested in practice assignments (and tests), they are available as pdf downloads in the "Other Information" section of the Course Description.

20 sep 2012: The Membrane Structure and Function lecture notes are available.

I have mounted them on the Moodle website.

21 sep 2012 update: I've been getting some questions from students about additional resources to help them with the material. For some, I've encouraged them to take advantage of the Byrne and Schultz coursekit available in the bookstore. Even though it's targeted towards medical students, it does provide a simplified overview that should help students orient themselves. Course Notes are also available on this website: [pdf]. These focus on the mathematical derivations, and may provide students with more detailed guidance in this regard.

18 sep 2012: Assignments and Grading:

Below is the assignments and grading scheme decided by students this year (2012)

Take Home Assignments (10% each) (30% total)

Two term tests and the final exam (highest scoring 40%, middle scoring 20%, lowest scoring 10%) (70% total)
Term Test Dates are Thursday 18 October, and Tuesday 20 November.

In the event of a documented absence from a term test, the weight (10%) will be transferred to the final exam

10 sep 2012: Moodle calendar activated.

I activated the calendar on the Moodle website, so that you could add dates --either preferred test dates or dates of tests you have in other courses-- by clicking on the calendar month, then the 'New Event' button. I hope this will be helpful: Moodle website.

05 sep 2012: Course Information Handout.

Course Information --essentially a synopsis of information on this website is available as a [pdf]. Hard copies will be available tomorrow.

15 aug 2012: Course Calendar: Important Dates.

A calendar listing important dates is available as a [png] or [pdf]. Please note that the final date for announcing the final grade components is early this year (18 sep), so students will have to decide on assignments and grading fairly quickly (see Course Description section below). Please pay attention to scheduling of tests etc. in other course when deciding on the timing of tests in Membrane Transport.

29 jul 2012: The Moodle course website is active and available to students.

In the past, students have created a course-specific facebook page. The Moodle course website is meant to provide you with the same opportunity to have a forum for student discussion, if you so desire. Lecture notes will also be provided on Moodle.

27 jul 2012:

Berg: Random Walks in Biology
Byrne and Schultz: Membrane Transport. An Introduction to Membrane Transport and Bioelectricity)

York Bookstore website

21 aug 2012 Update:

04 apr 2012: The course scheduling has been mounted for the fall 2012 term (subject to revision). The course will be held in LSB (Life Sciences Building) Room 107 on Tuesday and Thursday from 8:30 to 10:00 AM.

2010

20 dec 2010: Thank you all for making this such an enjoyable course, and, best wishes on all your future transporting endeavours.

16 dec 2010: Second final exam update:

As promised, here are the pages of equations and constants from the draft final exam [pdf]. I don't anticipate any revisions.

07 dec 2010: The last case study will be on light-gated ion channels in algae.

Research on phototactic algae was what led to the discovery of light-gated channels, eventually harnessed for the biotech application of modulating neuronal activity. Here is a link to an overview of "Vision" in Single-Celled Algae.

02 dec 2010: The New York Times just published on a bacteria capable of living off of arsenic rather than phosphorus.

They describe a bacterium scraped from the bottom of Mono Lake in California, then grown in medium containing arsenic, supplanting phosphorus over time. Mono Lake is hypersaline with high arsenic levels. The formal paper was published in Science

02 dec 2010: A quick correction to today's lecture. Lara was right: pyranine is membrane impermeant, and is 'reporting' on the pH outside of the vesicles per the description from the source paper [gif].

30 nov 2010 The next case study will be on Archaeal transport.

David Valentine wrote an overview of Archaeal ecology and adaptations that provides a good overview of these extremophiles.

16 nov 2010: Here is another sample assignment for energetics analysis [png].

It may be useful in preparing for the second term test on Thursday 18 November during lecture time.

15 nov 2010: Here is a link to a brief explanation of the use of bioenergetics to ascertain the effectiveness of various transport mechanisms.

It comes from a Biophysics Online resource provided by the Biophysics Society: Thermodynamics Of Energy Transduction In Biological Membranes by William A. Cramer and Glenda M. Soriano

27 oct 2010: Here is another sample assignment for capacitance analysis [png].

Please understand that the assignment is presented as is (no warranties of any kind). The assignment requires you to select appropriate dimensions for an axon. The equations are not provided but are variations on the

charge = capacitance times voltage

equations presented in Tuesday lecture.

26 oct 2010: Here is a sample assignment for permeability ratio analysis [pdf].

Please understand that the assignment is presented as is (no warranties of any kind).