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First let me welcome you to The Molecular Control of Cell Function course. The course emphasises the diversity of roles played by protein molecules in the life of individual cells, tissues and organisms. We begin by looking enzymes, how they act and how they are regulated. This leads on to a discussion of how metabolic pathways are regulated, a topic that is further developed in one of the practicals. From there we will discuss metabolic disorders before covering some of the fundamental aspects of cell structural and functional organisation, progressing to a consideration of how cells interact with and respond to signals they receive from their environment. The final part of the course deals with how cells interact with adjacent cells and with the extracellular matrix.
The overall general aims are to enable students:
• To become knowledgeable about the fundamental roles played by selected proteins or groups of proteins in the working life of cells, tissues and organisms;
• To experience first hand some of the laboratory procedures that are used to acquire the information learned about in lectures. This will also serve the general function of increasing students’ level of experience in designing and performing laboratory work and in data interpretation; and
• To gain experience in preparing and delivering the subject to an interested audience in order to enhance personal communication and presentation skills.
Subject specific learning outcomes of the course
At the end of the course students should be able to:
• Describe how enzymes function using selected examples; to include the role played by metal ions and co-enzymes, enzyme kinetics, inhibition of enzyme activity
• Describe the actions of selected enzymes; to include chymotrypsin, aspartate- and metallo- proteases, impact on medicine
• Describe how enzymes are regulated; to include allosteric regulation, covalent modification, isozymes, precursor processing
• Describe the background rational and experimental evidence for the traditional concept of a “rate-limiting enzyme” in the regulation of flux through metabolic pathways
• Describe the concept of “metabolic control analysis” to explain how flux through metabolic pathways is regulated; to include the “flux control coefficient” of each enzyme in a pathway
• Discuss the concepts of chemiosmosis and intracellular homeostasis
• Describe the structural and functional features of selected membrane transport proteins
• Describe the mechanisms that regulate body mass and the resultant metabolic diseases that occur when these go awry
• Describe the current status of understanding of type 1 and type 2 diabetes mellitus
• Describe molecular mechanisms that regulate cell shape and movement; to include cellular cytoskeleton biochemistry
• Describe selected aspects of cell signalling including the operation of tyrosine kinase receptors, G-proteins, lipid-derivatives and calcium ions as second messengers, cell signalling in the immune system
• Define the nuclear receptor superfamily and describe the overall mechanism of action of steroid receptors and related non-steroid receptors (thyroid hormone, retinoic acid, vitamin D receptors)
• Explain the tissue specificity of hormone response as regards glucocorticoids and mineralocorticoids
• Describe the molecules and mechanisms that govern cell-cell adhesion and cell-matrix interactions
Students will also develop practical skills in data interpretation, communication (written and oral) as well as interpersonal and team-working skills. These represent transferable skills that will benefit students across a range of disciplines.
The aims of the course will be achieved through a combination of lectures, tutorials, practical classes and a Microsoft PowerPoint presentation.
1. KEEPING A BALANCE INSIDE THE CELL
Subject: How enzymes work
No. of Lectures: 3
Lecturer: Prof K Docherty
These lectures aim to explain our understanding of how enzymes function. We will consider how the catalytic efficiency of an enzyme relates to binding of substrate to the active site and the chemistry of the reaction catalysed. Throughout the series, the relationship between structure and function will be discussed. We will also consider how enzymes use metal ions or co-enzymes to carry out the reaction, and more complex organisation of enzymes in multi-functional enzymes and in multi-enzyme complexes.
• Studying enzymes in the laboratory, including the measurement of single and linked reactions. Measuring activity to gain insight into catalytic mechanisms.
• Proteases as examples of distinct but related mechanisms: chymotrypsin, cysteine proteases, aspartyl proteases, serine proteases
• Cofactors and coenzymes and their roles in catalysis.
Subject: Regulation of enzyme activity
No. of Lectures: 3
Lecturer: Prof K Docherty
These lectures will consider allosteric regulation of enzyme activity, reversible covalent modification and its hormonal control, stressing the regulatory significance and complementary nature of these mechanisms.
• Concept of allosteric regulation, with aspartate transcarbamoylase as the defining example of the separate location of active and regulatory sites.
• Reversible covalent modification. Phosphorylation of key enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase. Reciprocal control of metabolic pathways, including hormonal regulation of the balance of activities.
Subject: Regulation of enzyme activity: Metabolic Control
No. of Lectures: 2
Lecturer: Prof A J P Brown
Basic aspects of the flux control theory; worked example of the bacterial sugar phosphotransferase system as an example of its application to a complex pathway of interacting proteins that can be both substrates and enzymes.
Tutorial – reconstruction of flux through glycolysis and the TCA cycle.
Subject: Bioenergetics and Transport Processes-Membrane Transport
No. of Lectures: 3
Lecturer: Dr D Scott
The aim of these lectures will be to describe classes of proteins that transport solutes across the plasma membrane and to relate where possible the molecular features of these molecules to their transport function.
• Bioenergetics associated with membrane transport processes. An overview illustrating ways in which cellular metabolism may be coupled to transport function.
• The distinction between carrier and channel transporters. The distinctive differences in the way these two classes of transporter function and how this relates to their molecular arrangement within the plasma membrane.
• The aquaporins with special reference to AQP1, AQP2, and AQP3 and their importance for water transport in kidney function.
• The amiloride sensitive sodium channel. The principle structural features of this epithelial transport protein and their relation to its transport function in particular ion selectivity.
• Sodium dependent and sodium independent glucose transporters with particular emphasis on SGLT1, and GLUTS 1, 2 and 4.
• The ABC (ATP-binding cassette) superfamily of proteins with special reference to the eukaryotic multidrug resistance (MDR) protein and the cystic fibrosis transmembrane regulator.
Subject: Metabolic Diseases
No. of Lectures: 4
Lecturer: Prof K Docherty
The aim of these lectures is to give an overview of a living cell as a biochemically-integrated entity. Emphasis will be placed on understanding the mechanisms that regulate body weight and the diseases including type 1 and type 2 diabetes that result from defects in these lipostatic mechanisms
• Biochemistry of obesity including the central and peripheral control of body weight including the role of leptin, NPY, GLP-1 and ghrelin
• Overview of glucose homeostasis with emphasis on role of muscle, liver and adipose tissue and role of the endocrine and nervous system
• Type 1 diabetes as an autoimmune disease, including role of autoantigens in β cell destruction, animal models and prospects for vaccines.
• Genetics of type 1 diabetes and role of environmental factors
• Treatment of type diabetes including islet transplantation and stem cell
• Type 2 diabetes with emphasis on role of insulin resistance and β cell defects.
2. REACTING TO EVENTS OUTSIDE THE CELL
Subject: Receptors and Signalling Molecules
No. of Lectures: 6
Lecturer: Dr B Müller
Cell signalling, the mechanism of communication between cells in multicellular organisms, is important for growth and development. The responses to signalling range from altered gene expression, changes in metabolism to cell death. The aim of these lectures is to give an overview about mechanisms and cascades involved in signalling, and to discuss selected aspects in more detail. Disorders caused by defective signalling will also be discussed. Lectures will focus on
• G- protein coupled receptors and second messengers production
• Receptor tyrosine kinases, Ras protein activation and kinase cascades
• Cytokine receptors, JAKs and STATs
• TGFβ and NFκB signalling
• Lipid-derived second messengers and control of protein kinase B and protein kinase C
Subject: Receptors and Signalling Molecules: Steroid hormone receptors and related proteins
No. of Lectures: 4
Lecturer: Prof K Docherty
The aim of this series of lectures is to illustrate mechanisms by which small hydrophobic molecules are used as signals to control proliferation, differentiation and cellular metabolism in multicellular organisms. The lectures will discuss the ever-growing family of nuclear receptors by focussing on steroid hormone receptors (glucocorticoid receptor, oestrogen receptor) and key non-steroid receptors (including thyroid hormone, retinoic acid, and vitamin D3 receptors). Our increased understanding of nuclear receptor mechanisms of action through domain swapping experiments, transfection studies and reconstitution of receptor activity in the yeast Saccharomyces cerevisiae will be discussed. The differential response of tissues to circulating hormones through metabolism, together with the implications for human health of disrupting nuclear signalling will also be considered.
• Introduction to nuclear receptor superfamily
• Overview of nuclear receptor structure and function
• Tissue specificity of the hormone response
• Glucocorticoids and mineralocorticoids exert different metabolic effects on target tissues (i.e. energy balance and salt balance respectively) but glucocorticoids can bind to both the glucocorticoid receptor and the mineralocorticoid receptor. The role of 11-beta-deydrogenase in regulating the specificity of mineralocorticoid hormones action.
• Defects in nuclear receptor signalling leading to genetic disease
• Resistance to androgens, thyroid hormones and vitamin D3
• Defects in metabolising enzymes
3. BEYOND THE SINGLE CELL
Subject: Regulation of cell shape and movement
No. of Lectures: 6
Lecturer: Prof I McEwan
• Structure and function of intermediate filaments, microfilaments and microtubules.
• Function of components of cytoskeleton in cell structure, shape, motility and chromosome movement.
• Regulation of assembly, role of associated proteins including motor proteins (kinesin, dynein)
• Dynamic nature of these components.
Subject: Multicellularity: cell-cell and cell-matrix interactions
No. of Lectures: 4
Lecturer: Prof I McEwan
The aim of these lectures is to discuss the processes of cell-cell adhesion, the structures and functions of cell-cell junctions, the biochemistry of the extracellular matrix, and the nature of cell-matrix interactions. Throughout, the emphasis is on how the matrix affects cell behaviour, and what happens when cell-matrix interactions malfunction.
• Cadherins and immunoglobulin superfamily proteins are major cell-surface glycoproteins concerned with cell-cell adhesion within tissues. Selectins are cell-surface glycoproteins concerned with the adhesion of circulating cells to blood-vessel walls.
• The three major types of cell-cell junctions are occluding (tight) junctions; anchoring junctions including cadherin-involving adherens junctions and desmosome junctions; and communicating (gap) junctions.
• Major components of the extracellular matrix are glycosaminoglycan-containing proteoglycans, collagen, elastin, fibronectin and laminin.
• Cell-surface integrin glycoproteins are key components in connecting the cytoskeleton with the extracellular matrix. They communicate information between matrix and the cytoskeleton, and transmit information from the outside of the cell to the inside, through a series of recently-discovered pathways involving secondary messengers.
There will be two practical/lab classes as part of the course:
1. Protein Purification and Characterisation practical (KD)
2. Metabolic Pathways – Control of Flow (SM)
Practical skills will be acquired during the laboratory class, including the ability to obtain record, collate and analyse information in the laboratory. Students have much more input to these laboratory classes, in terms of decision making, in this level 3 course than previously.
Laboratories are potentially dangerous places, and certain codes of conduct must be observed to maximise the chances of you and everyone else working safely. At the start of the practical exercise all students will be instructed on the correct behaviour and level of safety expected in the laboratories. All students are expected to possess and wear a laboratory coat during practical classes. Additional forms of personal protection including safety glasses and disposable gloves will be provided. Students will also be instructed on the correct handling of chemicals and biological materials used as part of the practical. You have an important part to play in ensuring your own and others’ safety. Think carefully before you undertake any task, and if in doubt about safety, ask the supervisory staff.
Protective clothing. You must possess and wear a laboratory coat during practical classes. Do not carry sharp objects in your clothing. Ensure that footwear is non-slip and is able to protect your feet from falling glassware, etc. Safety spectacles are available and should be worn at all times in practical classes. Disposable safety gloves are also available: make sure that they are worn whenever chemical reagents of any sort are being used.
Fire and Accident precautions. During the first classes of the session, the class supervisor will tell you where the fire extinguishers, fire alarm, fire exits and first-aid equipment are located in the main rooms in which you will be working. If you enter an unfamiliar room, note where these facilities are before starting work. Any accident involving personal injury must be reported to the member of staff supervising the class.
Health. If you have difficulties such as epilepsy, diabetes, a heart condition, or colour blindness, which might affect your performance or safety in the laboratory, please tell the Course Co-ordinator at the start of the session. The information, if desired and where practicable, can remain confidential.
All items of course work should be handed in at the time indicated at the Polwarth Building teaching laboratories, 2:054. Here you will find a box marked with the course number (BC3503) and you should place your work in this box. This box will be removed at 12.30 p.m. on the day the course work is to be handed in and work appearing after this time will be deemed to be late.
Please take care to ensure that your work is placed in the correct collection box. Failure to do so will incur the same penalty as if your work was handed in late. Seek the advice of a member of staff if you realise that you have placed your work in the wrong box as the boxes are tamper-proof and you should not attempt to recover the work yourself.
Work handed in late must be deposited with the Course Co-ordinator (KD) with a written explanation attached. Note: without a medical certificate only exceptional reasons will be acceptable so that no penalty will be incurred.
Please inform your Course Co-ordinator (KD) immediately if you anticipate problems with handing in your course work.
Each student should own a personal copy of at least one book from this list.
Lodish H et al, Molecular Cell Biology (Freeman, San Francisco)
Alberts et al., Molecular Biology of the Cell (Garland)
Berg, Tymoczko & Stryer, Biochemistry (Freeman, San Francisco)
Nelson, D L & Cox M M, Lehninger: Principles of Biochemistry (Worth, New York)
Garrett RH and Grisham CM, Biochemistry (Cengage Learning).
The University has strict regulations on plagiarism. If you are unsure about what constitutes plagiarism read the University guide on plagiarism at:
http://www.abdn.ac.uk/writing
Copying or plagiarising another person’s work, either from other students or published material in books or papers and submitted as your own for assessment is considered a form of cheating. This is considered by the University to be a serious offence and will be penalised according to the extent involved and whether it is decided there was an attempt at deliberate deception, or whether bad practice was involved. If you do use information or ideas obtained from textbooks or other published material you must give a precise reference to the source both at the appropriate point in your narrative and in a list of references at the end of your work. Direct quotations from published material should be indicated by quotation marks and referenced in the text as above.
The course is assessed in two ways:
1. CONTINUOUS ASSESSMENT (20% of total): This will be made up of marks from the written reports and oral presentations as follows:
1. Protein Laboratory report + presentation 10% (8% report and 2% talk)
2. Chemiosmosis Laboratory report 4%
3. PowerPoint Presentation 6% (4% report and 2% talk)
2. WRITTEN EXAMINATIONS (80% of total): This will be of three hours duration and will be held at the end of the 12 week second half-session in May/June. The written examination paper will be divided into two sections, each with a choice of four questions. You will be asked to answer two questions from each section. All questions are of equal weighting. Details regarding Time and Place will be given to you in plenty of time.
Oral examinations may be arranged for a few students who fall close to the borderlines of Pass/Fail or possibly the Honours entry standard. The list of students for oral examination will be posted on the 3rd year notice board within 5 working days after the written examination in June, and the oral examinations will be held shortly thereafter. Each exam will last for 15-20 minutes and will normally be conducted by Professor Kevin Docherty and another member of staff who taught on the course. Any aspect of the course may be discussed. The outcome of this oral examination will be posted on the 3rd year notice board the following day. Students are responsible for checking whether they will be required for an oral examination by regularly monitoring the notice board in the days following the written examination. Students should also note that candidates asked to attend for oral examination and failing to do so will be assigned their pre-oral (failing) CAS assessment. It is important, therefore, that you do not plan to take a holiday at this time unless you can be certain that you will not be required to attend an oral examination.
The total assessment of the course, recorded as a single CAS mark, is based on two elements of the course as follows: Continuous assessment marks contributing 20% of the total and the written examination contributing 80%. To achieve an overall pass for the course you must obtain a CAS score of 9 or better for the entire course AND you would be expected to also pass the written examination with a score of 9 or better.
The re-sit examination will be based on the written paper as above and the previous continuous assessment marks achieved during the course.
Prof Alistair Brown
Prof Kevin Docherty
Prof Iain McEwan
Dr Samantha Miller
Dr Berndt Mueller
Derek Scott David Stead
The University is keen to help you successfully complete your studies. If at any time you feel you need assistance, there is a range of support services available to help you. These include support to help with unexpected and/or exceptional financial difficulty, support for disabled students and academic learning support through the Student Learning Service. Further details about all these services are available at http://www.abdn.ac.uk/studenthelpguide/.
We value student’s opinions in regard to enhancing the quality of teaching and its delivery; therefore in conjunction with the Students Association we support the operation of a Class representative system.
The students within each course, year, or programme elect representatives by the end of the fourth week of teaching within each half-session. In this course we operate a system of course representatives. Any students registered within a course that wishes to represent a given group of students can stand for election as a class representative. You will be informed when the elections for class representative will take place.
What will it involve?
It will involve speaking to your fellow students about the course you represent. This can include any comments that they may have. You will attend a Staff Student Liaison Committee and you should represent the views and concerns of the students within this meeting. As a representative you will also be able to contribute to the agenda. You then feedback to the students after this meeting with any actions that are being taken.
Training
Training for class representatives will be run by the Students Association. Training will take place in the fourth or fifth week of teaching each semester. For more information about the Class representative system visit www.ausa.org.uk or email the VP Education & Employability vped@abdn.ac.uk
The University operates a system for monitoring students' progress to identify students who may be experiencing difficulties in a particular course and who may be at risk of losing their class certificate. If the Course Co-ordinator has concerns about your attendance and/or performance, the Registry will be informed. The Registry will then write to you (by e-mail in term-time) to ask you to contact their office in the first instance. Depending on your reason for absence, the Registry will either deal directly with your case or will refer you to your Adviser of Studies or a relevant Support Service. This system is operated to provide support for students who may be experiencing difficulties with their studies. Students are required to attend such meetings with their Adviser of Studies in accordance with General Regulation 8.
Set criteria are used to determine when a student should be reported in the monitoring system. You will be asked to meet your Adviser if any of the following criteria apply for this course:-
either (i) if you are absent for a continuous period of two weeks or 25% of the course (whichever is less) without good cause being reported;
or (ii) if you are absent from two small group teaching sessions (e.g. tutorial, laboratory class) without good cause;
or (iii) if you fail to submit a piece of summative or a substantial piece of formative in-course assessment by the stated deadline'
If you fail to respond within the prescribed timescale (as set out in the e-mail or letter), you will be deemed to have withdrawn from the course concerned and will accordingly be ineligible to take the end-of-course assessment or to enter for the resit. The Registry will write to you (by e-mail in term-time) to inform you of this decision. If you wish consideration to be given to reinstating you in the course you will require to meet with the Convener of the Students' Progress Committee.
Students who attend and complete the work required for a course are considered to have been awarded a ‘Class Certificate’. Being in possession of a valid Class Certificate for a course entitles a student to sit degree examinations for that course. From 2010/11 class certificates will be valid for two years and permit a total of three attempts at the required assessment within that two year period i.e. the first attempt plus up to two resits.
You will receive a University e-mail account when you register with the University Computing Centre. The University will normally use e-mail to communicate with you during term-time. These e-mails will be sent to your University e-mail account, which you can access using Eudora or SquirrelMail.
It is your responsibility to check your e-mail on a regular (at least weekly) basis and to tidy the contents of your e-mail inbox to ensure that it does not go over quota (see http://www.abdn.ac.uk/diss/email/mailquota.hti for guidance on managing your e-mail quota). It is recommended that you use your University e-mail account to read and respond to University communications. If you already have a non-University e-mail account that you use for personal correspondence, it is possible to set up automatic forwarding of messages from your University e-mail account to your personal e-mail address (see http://www.abdn.ac.uk/studentmail/howto/) but, should you do so, it is your responsibility to ensure that this is done correctly. The University takes no responsibility for delivery of e-mails to non-University accounts.
You should note that failure to check your e-mail or failure to receive e-mail due to being over quota or due to non-delivery of an e-mail forwarded to a non-University e-mail account would not be accepted as a ground for appeal. For further information on appeals procedures, please refer to;
http://www.abdn.ac.uk/registry/quality/appendix5x18b.pdf
Tutorials
There is no assessment for these, but some preparation work may be required. Some information regarding tutorials may be given to you at the lectures or will appear on the notice board. The tutorials will extend student opportunity to analyse data, understand course material and make interpretations of the work published in the literature.
a) Interpretation and analysis: how to read a scientific paper
b) Regulation of metabolism
c) Signal transduction
Literature Research and Group Work (PowerPoint Presentation)
Students will be divided into groups at the start of the course and each group will be asked to present their chosen topic. Assessment will be based on this group presentation and an individual written report by each student.
External Examiner
Professor J Ian Mason, University of Edinburgh
