PROJECT TITLE: Understanding the role of genetic variation in ERp57 in health and disease

 

INTRODUCTION TO THE PROJECT

 

ERp57 is a multifunctional protein which is upregulated in neurodegenerative disorders including Amyotrophic lateral sclerosis and Creutzfeldt Jacob’s disease. Erp57 forms part of the major histocompatibility complex class (MHC) I peptide-loading complex and thus has an essential function in ensuring immune surveillance of our cells and immune detection of non-self antigens. ERp57 is a member of the protein disulphide isomerase family and also plays a role in the oxidative folding of glycoproteins in the endoplasmic reticulum. Oxidative folding is an essential function for all eukaryotes whereas MHC molecules are only found in some chordates (incl. fish, amphibians, birds and mammals). This means that the protein must originally have had a function in protein folding and later adopted its role in immunity.

 

Perturbation of the flow of proteins through the ER is known to affect neurodegeneration and hence variations in proteins known to affect this flow are likely to affect susceptibility to disease. We have unprecedented knowledge of human genetic variation through projects such as the 1000 Genome project. However, while variations are recoded and made available through databases they are often poorly annotated with scope for further exploration.

 

This project will look at how ERp57 has evolved to carry out two distinct functions and whether known genetic variation is likely to affect the function in one or the other role and this is likely to play a role in neurodegeneration.

 

AIMS OF THE PROJECT

 

Overall aim is to determine the extent of genetic variation in ERp57 and analyses potential consequences to the structure and function in either oxidative folding or peptide loading of MHC I with a particular focus on neurodegeneration. In order to achieve this you will:

 

Critically review the literature on ERp57’s involvement in neurodegeneration

 

Compare sequences of ERp57 from different species to build a picture of conserved and hence functionally important parts of the protein.

 

Classify known genetic variants of ERp57

 

Analyse the structure of ERp57and determine potential effect of genetic variants on the structure of ERp57

 

FORM OF CRITICAL ANALYSIS

 

Data analysis and evaluation relating to both sequence and structural data.

 

 

OTHER INFORMATION (methods to be used, starter references etc)

 

Andreu et al. (2012) “Protein disulphide isomerases in neurodegeneration: from disease mechanisms to biomedical applications” FEBS letters (586) 2826-34

 

Hetz and Mollereau (2014) “Distrubance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nature Reviews Neuroscience (15) 233-249

 

The 1000 Genomes Project Consortium (2015) “A global reference for human genetic variation.” Nature (526) p68-74

 

 

 Project Presentation Guidance

 

Instructions for authors

Project reports must be at least one-and-a-half-spaced. You must submit the anonymised version of your report electronically, in duplicate, via Moodle.

Make sure that you back-up your work. The failure of a computer or printer at this crucial time is not accepted as an excuse for late submission given the length of time you have had to write the final report. Failure to have a backup will simply mean lost marks as late submission is penalised in every case.

References

References should be cited according in a Vancouver style (numbered) or Havard style (author, date).

 

Additional Writing Guidelines:

Attention will be paid to the format of the presentation. The typical structure of summary/abstract, introduction, methods, results, discussion, conclusions (although conclusions are often included at the end of the discussion) and reference list may be suitable, but alternative formats are acceptable if more appropriate, discuss with your supervisor. All projects MUST contain a Methods section.

The summary/abstract should consist of one or two paragraphs (not more than a page) and be intelligible on its own, without reference to the main text. Written sections should be divided into sections logically and figures, tables, subheadings etc. should be used if they add clarity. Sources of information must be given in a reference list at the end of the report and must be referred to where appropriate in the text. It is also a good idea to list the other people you have had to contact in order to gather data.

Total length of the project will depend very much on the project and it is not felt helpful to define these precisely. However, a total length of 10,000 words MUST NOT be exceeded. Details of what is and is not included in the word count, plus penalty details for over-length reports are provided in a link on the Moodle page. 10,000 is a MAXIMUM, and not a target. At SLS, there is, and never has been, a 10% either way rule.

The introduction should discuss the aims of the project and the method of approach and should provide a review of the relevant literature. This should show that you have a reasonable knowledge of published work and can evaluate it.

The methods section should give an account of the procedure, such that an independent researcher with knowledge of the field could repeat the work. Previously published procedures need not be described in full; refer to the papers in question.

The results section should describe the results you obtained but you should avoid being drawn into discussing the significance of the results unless absolutely essential. Tables and figures in the results section should present information clearly. An explanation of the object of every experiment mentioned should appear in this or another section. Don’t duplicate results in the form of a table and figure. The Results section should describe the outcome of your procedures but the significance of the outcome should be in the Discussion.

Unlike in the results section which should be descriptive, the discussion section should be used to marshal and discuss the results. Inferences should be drawn and the relationship to other work discussed. This section should avoid repetition of the results section, which it will happen if you can understand the difference between describing results and discussing their relevance.

If there is a lot more useful information you wish to convey then use Appendices, but be aware that Appendices do not have to be read.  Reports that are beyond the word limit WILL be penalised, regardless of what your project supervisor may tell you. Most excessive reports presented would benefit from editing and pruning. Some supervisors may say it doesn’t matter what length your report is, however, in the interests of equality the Director of UG Studies has the final say and projects WILL be penalised regardless of supervisor’s advice.

APA

 

 

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