Difference between revisions of "Talk:2012 Group 5 Project"

From CellBiology
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# Frizzled-related proteins can be used as natural antagonists to manage the Wnt pathway.
 
# Frizzled-related proteins can be used as natural antagonists to manage the Wnt pathway.
 
# A “recombinant adenovirus (Ad-CBR) that constitutively expresses the B-catenin binding domain of APC” <ref><pubmed>15578921</pubmed></ref> was developed, enabling APC to maintain its function of B-catenin degradation.
 
# A “recombinant adenovirus (Ad-CBR) that constitutively expresses the B-catenin binding domain of APC” <ref><pubmed>15578921</pubmed></ref> was developed, enabling APC to maintain its function of B-catenin degradation.
# Monoclonal antibodies are being used against Wnt proteins induce apoptosis in cancer cells <ref name=PMID15578921/>.
+
# Monoclonal antibodies are being used against Wnt proteins by inducing apoptosis in cancer cells <ref name=PMID15578921/>.
  
  

Revision as of 16:09, 15 May 2012

--Mark Hill 11:46, 4 April 2012 (EST) As of Wed 4th April (week 5) other than the requested individual assessment references there is nothing on your project page (except the template sub-headings) or discussion page (other than allocation of work) that indicates that you are carrying out the research work on your project . I remind you of the assessment criteria and my expectation of ongoing demonstrable contributions.

  • The key points relating to the topic that your group was allocated are clearly described.
  • The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
  • Content is correctly cited and referenced.
  • The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.
  • Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
  • Relates the topics and content of the Wiki entry to learning aims of cell biology.
  • Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer’s wiki.
  • Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
  • The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
  • Develops and edits the wiki entries in accordance with this sites wiki guidelines.

Peer Review

what was done Well:

  • Although I didn't get the Joke of the image just before the intro, it was guite creative and catchy. Gives this page that X factor.
  • Mechanism of action diagram clarified everything in the text and it was highly relevant. It was a student drawn image which is a rare sight on other pages.
  • The movie in Mechanism of Action was educational. I understood the text a lot better after viewing
  • The disease section gave a lot of detail but it clearly linked the mutations of Wnt with the pathogenesis of the diseases.

Improvements needed:

  • Disease section - can you give some background information for each disease - such as epidiomology and symptoms? what happened to the references?
  • 'Key players table' doesn't seem complete - what happened to the structures of Dsh, axin and Gsk-3B?

  • Clever, creative intro.
  • History- great, nice detail, looks like someone put a lot of effort into it.
  • Mechanism of action, is another great section. info is in short and simple sentence layout (following Marks lecture material) i think its smart and clever thinking- you don't want to further elaborate i think the about of info is enough. nice picture, wish it could have more colour to it though- make it more appealing. MOVIE is a great idea- but very detailed like you warned
  • Disease table is also good, i like how you have little bit of information under each column makes it easy to read and understand. Dont know what has happened with ur references in this section.
  • This table under Key players in Wnt/β-catenin Signalling is nice work, will be good source of info when complete
  • Embryonic dev. is another clever interesting section you have added, i was interested in reading it.

-

Pros

  • great extensive history section
  • good layout that was very easy to read
  • most sections very well cited/referenced
  • great overall,polished project with interesting info

Cons

  • diseases associated section not cited properly

Possible improvements

  • basic info about b-catenin i.e. structure. The picture is great at showing the structure but having this info reiterated in writing would make it clearer.
  • embryonic development headings seems a little out of place. Should it be under a current research section? With other current research taking place/recent findings (not a big deal)

The introduction is clear and well-written. It gives a good overview of what will be discussed in further details throughout your project.

The history has an incredible amount of information. Credit on those who researched it all! When it comes to the picture displayed in the history section, please provide information whether or not you are classified as being an 'authorised user', as the copyright statements mentions 'Authorized users of Genes & Development may view, reproduce, or store copies of articles for the purposes of scholarly, research, educational, and individual use only'.

The mechanism of action is easy to understand and has a good amount of detail to it. The student picture in particular gives me as a reader a clear comprehension of what happens during the 'on' and 'off' state. This complements the text well. Please do note that you got inspiration for this picture from another source, hence the copyright statement will need to be provided. Your subheading on tumour cells might seem more logical in the abnormal function section, as I expect to read only the normal function in the mechanism of action.

The section on diseases looks very attractive with the table and 2 pictures. You might want to expand upon the treatment subheading - only to a minor extend though. Maybe give us some more information (if available) on what step of the abnormal signalling it affects in order to help relieve or cure the disease.

Great idea to provide the readers with the key players in the signalling pathway! However, to me it would make more sense if you were to put this section behind your history and in front of your mechanism of action. Just so that we get a general overview of what is involved before we read how they are involved. Also, some parts of the table were not visible, eg. structure of Dsh, Axin, GSK3beta, diversin. If information is unavailable then please mention this. Pictures in the table were very helpful.

Embryonic development is very important when it comes to the functioning of the WNT/beta-catenin pathway. Again, it might be good to rearrange your format - most ogical to me would be reading this section after reading about the mechanism of action and before the diseases section.

Your section on future directions seemed a bit rushed. There is no paragraph format, only dotpoints. If you are planning on listing them, then at least provide a brief statement saying what it is exactly that you are listing, eg. current research being undertaken, future research and hypotheses yet to be attempted, etc.

Your glossary seems good, although you could always expand upon that. With regards to the references I can see that a lot of research has been done. Please be aware of cite errors (eg. #63) and references which have been listed twice (eg. #74 and #75).

Overall, well done.



A very well written introduction, in addition to the image at top makes the reader wanting to read more, so well done. The History is extensive, and organised which is great. However, what is "Figure 2 doing next to the history.

Overall structure of the β-catenin/XAxin-CBD complex" doing next to the history?? The referencing for the history is great though.

The mechanism of action is extensive, and the detailed referencing makes the section look complete. I am glad to see that you have included a hand drawn image next to mechanism of action, and it easy to understand which is great. The external link which leads to the movie is a great idea, adding another movie for the history or a different section would also be beneficial.

However, the subheading tumor cells does not belong under the mechanism of action heading. It is good to see that you have included both the on and off state, and have explained the difference pathways

The use of tables and images to explain Diseases associated with Wnt/β-catenin signalling is a great idea. The images found here all have correct references and the right copyright information which is great to see. The Glossary makes everything clear, and it seems to be a great idea to include the abbreviation.

However, what you might consider is adding the meaning of the abbreviation within brackets after the word within the text. At least that way readers wont have to continually scroll up and down.

The external links are great sources. They had some information which I believe you could benefit from. One thing I failed to find is current and future reasearch. Please include that section, as the rest seems very good.

And the reference list is extensive. Good luck with the rest of the assignment.


Group 5's Discussion Board

As described above, the Wnt/ β-catenin signalling pathway plays a critical role in development, stem cell regulation and cellular processes such as proliferation and migration. Thus mutations in components of this pathway have been associated with cancers, hereditary disorders, developmental defects and other diseases.


For a comprehensive list of human diseases associated with mutations of the Wnt signalling components, please refer to Table 1 in the following article: Wnt/β-catenin signaling: components, mechanisms, and diseases[1]


Wnt/B-Catnenin Pathway and the Onset of Cancer

The high number of repressor genes involved in the Wnt-B-catenin pathway indicates that it is imperative for this pathway to be tightly regulated. [2] These repressor genes include APC, Axin 1 and Axin 2. Given the pathways involvements in the regulation of stem cell choice to proliferate or self renew, there is a strong correlation between mutations in these genes and the onset of cancer. The table below describes in further detail some mutations of the Wnt signalling pathway and associated cancers.


Mutations of the Wnt signalling pathway and associated cancers

Gene Normal function Effects of mutation Associated cancers [3]
B-catenin Primary Wnt effector. Acts as an oncogene. In the nucleus, B-catenin functions as a cofactor for TCF transcription factors which specify a subset of genes responsible for determining cell fate and regulation of proliferation. [3] Any mutations that inhibit its destruction motif would cause constitutively active B-catenin signalling, leading to excessive stem cell renewal and proliferation, predisposing the cells to the formation of tumours. [4]
  • Colorectal cancer
  • Prostate cancer
  • Uterine endometrial cancer
  • Melanoma
  • Hepatoblastoma (liver cancer)
  • Medulloblastoma (brain cancer)
  • Pancreatoblastoma (pancreatic cancer)
  • Ovarian carcinoma
  • Thyroid carcinoma
  • Pancreatic carcinoma
  • Hepatocellular carcinoma
  • Lung adenocarcinomas
  • Esophageal adenocarcinomas
  • Synovial sarcoma
APC Facilitates B-catenin degradation; acts as a tumour suppressor Mutational inactivation of APC inhibits degradation of B-catenin, leading to the over-stabilisation and accumulation of b-catenin in the nucleus of the cell.


Familial Adenomatous Polyposis (FAP)

  • Hereditary cancer syndrome caused by a germline APC mutation whereby one defective allele is inherited. [5][6]
  • Effect: large numbers of adenomas or polyps (benign out growths) are developed in the colorectum. [3] Inevitably, some of these polyps progress into cancers.
  • “10% of FAP patients display a deletion of AAAAG in codon 1309”. [3]


Colorectal Cancer (CRC)

  • Loss of function in both APC alleles
  • In intestinal epithelial cells the constitutive B-catenin/Tcf4 complex leads to unrestrained production of crypt stem cells, resulting in cancer. [7]
  • “Up to 85% of all sporadic CRCs have mutations in APC”. [3]
  • Colorectal cancer
  • Prostate cancer
  • Melanoma
  • Hepatoblastoma
  • Medulloblastoma
  • Ovarian carcinoma
  • Pancreatic non-ductal acinar cell carcinomas
  • Synovial carcinoma
  • Desmoid tumor
  • Gastric adenoma
  • Breast fibromatoses
Axin 1 & Axin 2 Serve as scaffolding components for the B-catenin degradation complex. Acts as a tumour suppressor. Mutational inactivation of Axin 1 or Axin 2 inhibits degradation of B-catenin, leading to the over-stabilisation and accumulation of b-catenin in the nucleus of the cell.
  • Ovarian carcinoma
  • Hepatocellular carcinoma
  • Medulloblastoma
  • Predisposition to colon cancer [8]

Treatment:

There is a large focus on finding more effective means of treating and preventing cancer. Current researchers are looking at inhibiting various components of the Wnt/B-catenin pathway to prevent the proliferation of cancer. Such treatments include:

  1. Small molecule inhibitors can be used to block the interaction between B-catenin and TCF, thus preventing constitutive transcriptional activities that lead to the proliferation of cancer. [9]
  2. Non-steroidal anti-inflammatory drugs (NSAIDs) function by interfering with B-catenin/TFC-dependent transcription, and have proven promising for the prevention of colorectal cancers. [10]
  3. Frizzled-related proteins can be used as natural antagonists to manage the Wnt pathway.
  4. A “recombinant adenovirus (Ad-CBR) that constitutively expresses the B-catenin binding domain of APC” [11] was developed, enabling APC to maintain its function of B-catenin degradation.
  5. Monoclonal antibodies are being used against Wnt proteins by inducing apoptosis in cancer cells [12].


Sorry, I realized that I copied the wrong table into the wiki page (I made one copy with the correct referencing format and one which I could use on Microsoft word).

I'm trying to find photo's of each disease and more information on treatment options. Does anyone know of a website that allows you to search for images in journal articles?

--Z3289738 11:43, 14 May 2012 (EST)


Umm Nat we're not supposed to be working on the wiki page this week. Otherwise the comments from peer review would not be consistent, if the first reviewer saw a different product to the last one.

You can save your progress offline, and transfer it after our next lab.

--Z3336051 19:40, 13 May 2012 (EST)




Hey, I found a list of areas for future research in my article so I copied it over to that section.

Its looking good guys :)

--Z3289738 15:37, 10 May 2012 (EST)



Hey guys, I was also having issues uploading things onto the wiki, everytime I edited something it would save and then disappear - very frustrating! Everythings up now so hopefully it will stay there.

As for everything below I just needed to paste it somewhere while I edit it further

Notes

Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases [1]

  • Signaling by the Wnt family of secreted glycolipoproteins is one of the fundamental mechanisms that direct cell proliferation, cell polarity, and cell fate determination during embryonic development and tissue homeostasis (Logan and Nusse, 2004). As a result, mutations in the Wnt pathway are often linked to human birth defects, cancer, and other diseases (Clevers, 2006). A critical and heavily studied Wnt pathway is the canonical Wnt pathway, which functions by regulating the amount of the transcriptional coactivator β-catenin, which controls key developmental gene expression programs.
  • Given the critical roles of Wnt/b-catenin signaling in development and homeostasis, it is no surprise that mutations of the Wnt pathway components are associated with many hereditary disorders, cancer, and other diseases (Table 1).
  • Association of deregulated Wnt/β-catenin signaling with cancer has been well documented, particularly with colorectal cancer (Polakis, 2007) (Table 1). Constitutively activated β-catenin signaling, due to APC deficiency or β-catenin mutations that prevent its degradation, leads to excessive stem cell renewal/proliferation that predisposes cells to tumorigenesis.
  • Mutations of β-catenin at and surrounding these serine and threonine residues are frequently found in cancers, generating mutant β-catenin that escapes phosphorylation and degradation (Table 1).


Caught up in a Wnt storm: Wnt signaling in cancer [3]

  • The Wnt signaling pathway, named for its most upstream ligands, the Wnts, is involved in various differentiation events during embryonic development and leads to tumor formation when aberrantly activated. Molecular studies have pinpointed activating mutations of the Wnt signaling pathway as the cause of approximately 90% of colorectal cancer (CRC), and somewhat less frequently in cancers at other sites, such as hepatocellular carcinoma (HCC).
  • Greater than 90% of all CRCs will have an activating mutation of the canonical Wnt signaling pathway, ultimately leading to the stabilization and accumulation of β-catenin in the nucleus of a cell.
  • Fig. Schematic representation of a colon crypt and proposed model for polyp formation. At the bottom third of the crypt, the progenitor proliferating cells accumulate nuclear β-catenin. Consequently, they express β-catenin/TCF target genes. An uncharacterized source of WNT factors likely resides in the mesenchymal cells surrounding the bottom of the crypt, depicted in red. As the cells reach the mid-crypt region, β-catenin/TCF activity is downregulated and this results in cell cycle arrest and differentiation. Cells undergoing mutation in APC or β-catenin become independent of the physiological signals controlling β-catenin/TCF activity. As a consequence, they continue to behave as crypt progenitor cells in the surface epithelium giving rise to aberrant crypt foci.

--Z3289738 11:22, 10 May 2012 (EST)



Hey guys, really sorry but I don't know what happened to the last bit of our wiki page! >.< I was still adding to the glossary this morning, and I just went back to check out our page, and now it's missing!! I've tried undoing a few things but it hasn't come back...

I actually have to leave home for class now, and I won't be free right up until the lab begins (when the page will most likely be locked). I'm really sorry to ask the favour, but could someone please figure out how to bring back the lost data? I haven't kept an offline copy of the current/future research and glossary (and everything else beyond it)...

--Z3336051 21:51, 9 May 2012 (EST)


Hi Lee,

Actually I was doing the history :) -- Nat's taking care of the diseases associated with the signaling pathway. To be honest, the figure doesn't have too much to do with the history but it was the only relevant one I could find that could be posted on the website. I don't know if you noticed but all the references for the history come from big journals like Nature and Cell and so you have copyright issues.

I can try to relate the history to the figure or vice versa so things make more sense. Good job everyone!

Cheers, Sara --Z3333421 11:21, 7 May 2012 (EST)


Hi Nat (I think you're doing history now right?)

I noticed you posted up a figure of the β-catenin/XAxin-CBD complex. Since we're all madly posting content right now I understand why you haven't written up the explanation for the figure yet. I know no one else in our group has either (including me) but I ask about this one in particular because I'm a bit confused as to what it has to do with history.. I want to better understand what everyone else is doing, because it'll be more helpful than not for me to track what everyone else is doing, in putting together content for my section.


And to everyone else, especially Sara who has put in so much effort (and more than what she needed to!), sorry I haven't been contributing much so far. Been drowning in more work than I expected. This week however, cell bio will be my first priority subject in terms of workload. Partly because our page will be locked for peer evaluation by Thursday anyway.


Keep working hard everyone! Our page is slowly but surely taking form :) And please give me honest feedback as to anything you feel I should be doing but aren't doing currently. I would rather a group member point it out first so it can be fixed before someone else catches on during peer review assessment.


Cheers, Lee --Z3336051 21:19, 5 May 2012 (EST)


Thanks Sara for the table! It'll be a big help to decluttering my content.

--Z3336051 15:08, 4 May 2012 (EST)



Hey Sara, I can't work out how to create a table! If you have time, can you please one with these headings

- disease
- description
- causes
- symptoms
- treatment
- picture

Thanks :)


--Z3289738 15:26, 3 May 2012 (EST)



Hey guys, I've just edited some of the history, added a new pic (that wasn't copyrighted), updated the glossary and added content to embryonic development.

Lee, I also added a table that might be helpful in organising the content for the key players section.

--Z3333421 13:09, 3 May 2012 (EST)


Thanks Sara, I've started editing the disease section so all good now :)


I've just added/modified the subheadings for the page. Natalie, which section would you like to swap diseases with?

--Z3333421 21:35, 20 April 2012 (EST)


Hi guys, I've just uploaded the history which is not quite finished yet and I have to add in the references cheers.

--Z3333421 09:42, 19 April 2012 (EST)


Hey guys, Here's another simple diagram of the Wnt signaling cascade (on the right)

File:The Wnt Signaling cascade, simplified.png
Figure._Schematic_representation_of_a_colon_crypt_and_proposed_model_for_polyp_formation [3]

See you tomorrow




Just found a pretty good diagram showing the "on" and "off" states of the Wnt signalling pathway

Sam --Z3332227 17:21, 18 April 2012 (EST)



I've just written up a few notes on Wnt/Beta-catenin signalling. I haven't added the references in yet and i'm still looking for some good diagrams that explain it simply.

Sam --Z3332227 15:48, 10 April 2012 (EST)



Hey everyone, so to make it official, the task assigned to us for our project pages this week has officially been to upload one image each onto the wiki. I add one extra goal for our group to achieve by the end of this mid sem break; to begin writing relevant information under our assigned subheadings, and sourcing our information from four articles, by referencing it correctly.


Keep posting here, to keep each other updated on each of our progresses, and to keep the thoughts flowing.

Enjoy your breaks!

Lee --Z3336051 21:22, 6 April 2012 (EST)



Hey guys, I found four articles relating to abnormal function of the pathway:

Paper 1

Taketo, M Mark. "Shutting down Wnt signal-activated cancer." Nature Genetics 36. (2004): 320-22. DOI: 10.1038/ng0404-320 <pubmed>15054482</pubmed>

In this article, New evidence suggests that Wnt signaling can be suppressed or further activated by upstream signals, even though the pathway seems to be constitutively activated by downstream mutations in cancer cells.


Paper 2

<pubmed>19619488</pubmed>

This article highlights some key aspects of Wnt/β-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications


Paper 3

<pubmed>15578921</pubmed>

This review discusses some of the strategies that are being used or can be explored to target key components of the Wnt/β-catenin signaling pathway in rational cancer drug discover.


Paper 4

<pubmed>12781368</pubmed>

This review considers the spectra of tumors arising from active Wnt signaling and attempts to place perspective on recent data that begin to elucidate the mechanisms prompting uncontrolled cell growth following induction of Wnt signaling.

--Z3289738 10:48, 29 March 2012 (EST)




Check this out. It's a website all about the Wnt pathway. It has a list of virtually all review articles on the pathway.

http://www.stanford.edu/group/nusselab/cgi-bin/wnt/wntreviews




<pubmed>9529612</pubmed> A review of the Wnt/beta-catenin pathway and the protein and receptor interactions involved.


<pubmed>9407023</pubmed> Outlines the evidence for the interaction of the Frizzled receptor with the Wnt protein.


<pubmed>15001769</pubmed> Explores the interrelationship between the Wnt, beta-catenin and cadherin pathways by examining the role of receptor activation and repression to control gene expression.


<pubmed>15652476</pubmed> Newer research made possible by advancements in imaging technology have better elucidated the finer interactions in the Wnt/beta-catenin pathway.


--Z3336051 23:36, 25 March 2012 (EST)




<pubmed>19619488</pubmed> Overview of the Wnt signaling pathway; ligands, agonists and antagonists and their interactions with Wnt receptors. Also mentions its implication in the development of human disease.


<pubmed>12775774</pubmed> Main extracellular antagonists of the Wnt signalling pathway - regulation of cell growth/differentiation.


<pubmed>19279722</pubmed> Involvement of Wnt signalling molecules in the control of embryonic development.


<pubmed>18392048</pubmed> Role of the Wnt pathway in proliferation, differentiation and apoptosis in adult tissues (and therefore oncogenesis).


--Z3332227 12:27, 25 March 2012 (EST)




Thank you so much Li! I'm happy with the allocations...here are my references for this week's homework


<pubmed>16793760</pubmed> This review article provides a concise overview of the Wnt/Beta Catenin Signalling which can used in the introduction.


<pubmed>15372092</pubmed> There are a number of clearly labelled diagrams in this article that can be used as a starting point for the student drawn image.


<pubmed>18673238</pubmed> This article provides an historical overview of the key events that shaped our understanding of Wnt/Beta Catenin signalling and hence can greatly aid the history section.


<pubmed>17081971</pubmed> This review also contains many simplified diagrams that can be used to support the student drawn image.

--Z3333421 22:32, 22 March 2012 (EST)




Unfortunately we didn't get notch signalling, so we'll go with Wnt/beta-catenin signalling? To Natalie, the reason we didn't go with JAK/STAT was because of the apparent lack of research available on it. Wnt/beta-catenin seems better understood.


The following is a recommended assignment of sections, so we can get to our homework which is to each find four references for our respective assignment sections.

If you would like to swap, these roles are negotiable, but keep in mind that our homework is due next week.

  • Introduction + History + pathway images (at least one drawn) - Sara
  • Normal Function - Sam
  • Abnormal Function - Natalie
  • Receptors involved + (if applicable)Proteins involved - Li

To Sara, I wasn't quite sure how to divide up the subheadings based on the roles you wrote down, but you're free to reassign if you can elaborate for me. The above is my attempt at filling in the details.

Finally, I will look after maintenance of page formatting. Come to me if you have any questions.

--Z3336051 16:46, 22 March 2012 (EST)




Hey guys, If we decide to go with notch signaling here's a really great diagram & description: http://www.cellsignal.com/reference/pathway/Notch.html

--Z3289738 14:28, 22 March 2012 (EST)

  1. 1.0 1.1 <pubmed>19619488</pubmed>
  2. <pubmed>15054482</pubmed>
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 <pubmed>12781368</pubmed>
  4. <pubmed>15054482</pubmed>
  5. <pubmed>1651562</pubmed>
  6. <pubmed>1651563</pubmed>
  7. Cite error: Invalid <ref> tag; no text was provided for refs named PMID22234609
  8. <pubmed>15042511</pubmed>
  9. <pubmed>19619488</pubmed>
  10. <pubmed>19619488</pubmed>
  11. <pubmed>15578921</pubmed>
  12. Cite error: Invalid <ref> tag; no text was provided for refs named PMID15578921