Talk:2014 Group 3 Project

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2014 Projects: Group 1 | Group 2 | Group 3 | Group 4

  1. Do not remove this notice {{2014 Project discussion}} from the top of the discussion page.
  2. Newest student comments should be entered at the top of this current page under the subheading "Student Discussion Area" (you cannot edit the sub-heading title).
  3. All comments should begin with your own signature button, that will automatically enter student number date/time stamp.
  4. Do not use your full name here in discussion, if absolutely necessary you may use first names only.
  5. Do not remove or edit other student comments.
  6. Use sub-headings if you want to add other draft information, images, references, etc.
  7. Only your own group members should edit this page, unless directed otherwise by the course co-ordinator.

Group Assessment Criteria

  1. The key points relating to the topic that your group allocated are clearly described.
  2. The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
  3. Content is correctly cited and referenced.
  4. 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.
  5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
  6. Relates the topic and content of the Wiki entry to learning aims of cell biology.
  7. 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.
  8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
  9. 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.
  10. Develops and edits the wiki entries in accordance with the above guidelines.

17 April 2014

Before the next practical class (after the mid-semester break) the following items must be completed:

  1. You have written draft text in the section(s) that you have been assigned by your group.
  2. Your text should include source references clearly identifying original research from review articles.
  3. Your section(s) must include at least one research/review image or student drawn image related to the section topic.
  4. You have clearly identified the work you have contributed on the project discussion page.

Projects will be presented by your group to the rest of the class at the beginning of the next practical. --Z3377989 (talk) 16:49, 20 March 2014 (EST)

--Z3418837 (talk) 16:50, 20 March 2014 (EST)

--Z5011434 (talk) 16:51, 20 March 2014 (EST)

Possible Topics

1) Nuclear Pore transport - z5011434

2) Shuttle Proteins - z5011434

a) Specific Type

3) Transcription Proteins to Cytoplasm - z3418837

4) 5' Cap and 3' Poly(A)Tail needed for mRNA transport out of nucleus - z3418837

5) Nucleolus involved in rRNA (does it go out to cytoplasm) -z3377989

6) Bidirectional Transport Mechanisms -z3377989

7) From cytoplasm to nucleus (what gets transported in?)

8) Signal Receptors

Research Articles

1.Select 4 reference papers related to your selected topic sub-section. Read these papers and write a brief description of their findings and relevance to the selected topic sub-section. The reference along with your description should then be pasted on both your group discussion page and your own personal page.

Article 1 - Charge as a Selection Criterion for Translocation through the Nuclear Pore Complex.

Nuclear pore complexes (NPCs) are porous structures that selectively control the components that pass through the nucleus to the cytoplasm and vice versa. A common understanding on the selective aspect of NPCs comes from the various diameter sizes that NPCs can occupy, however scientists have been focusing on another governing principle of translocation that they believe is related to charge. It is known that proteins that undergo rapid translocation are highly negatively charged, whereas proteins that are blocked from this translocation process are positively charged. Analysis has shown that, proteins that occupy the inside of the pore channel are net positively charged and transport receptors are negatively charged. This indicates that translocation rates within NPS are dependent on the electrostatic interactions between transport receptors and NPC due to an immense gain in energy. Overall, the investigation suggests that the negative charge plays a significant role in determining which components pass through the NPC.[1]

Article 2 - Role of Molecular Charge in Nucleocytoplasmic Transport.

Similarly to article one, this study focuses on the role of charge in the selectivity of Nucleocytoplasmic transport. It highlights the significance of phenylalanine-glycine (FG) nucleoporins (Nups) in creating a selective barrier with net positive charges in the nuclear pore complex. It is known that the positive charge accounts for the passive diffusion of small molecules and transport-receptor facilitated diffusion of cargo molecules. However, it was recently hypothesized that a negative surface charge plays a significant role in determining which components pass through the NPC. This study aims to unpack how these charge interactions may impact transport kinetics and spatial transport routes for both passive diffusion and facilitated translocation. By using high-speed fluorescence microscopy, scientists were able to determine that the electrostatic interactions between the negatively charged surface receptors and positively charged FG-Nups although increased the likelihood of NPC binding, did not reveal the nuclear transport mode or spatial transport routes. Instead, Nucleocytoplasmic transport was found to be dependent on molecular size, signal and surface charge and not one or the other.[2]

Article 3 - Higher Nucleoporin-Importin β Affinity at the Nuclear Basket Increases Nucleocytoplasmic Import.

For many years scientists have debated on whether the presence of an affinity gradient in NPCs for the import receptor Importin β increased or decreased Nucleocytoplasmic Import. However the answer to this postulation remained obscure. This study aimed to understand how this affinity gradient may have enhanced Nucleocytoplasmic Import by using agent based modelling (ABM) that looked at the association between rate constants and molecular binding. By employing different values of the affinity gradient, they have found that the rate of transport had increased by 10% compared to the pores lacking an affinity gradient. They also found that this effect was maximised at 200 µM for Importin β. Overall, this study highlighted the significance of Importin β Affinity in Increasing Nucleocytoplasmic Import rate.[3]

Article 4 - Assembly of Nsp1 Nucleoporins Provides Insight into Nuclear Pore Complex Gating.

Our current understanding suggests that the central transport channel which is a part of the NPC is formed by repeating subunits of FG-nups and serves as the selective barrier for incoming material. By analysing the spatial arrangements of nups, scientists can understand how NPC serves as a filter for macromolecules and allows for diffusion of small molecules below 40kDA. In this study, scientists used molecular dynamics to model the possible variations of Nsp1 (Nsp1-FG). They have discovered brush-like structures that consist of bundles that have been cross-linked to various nups. They have also found that transport factors are tightly associated with multiple FGS in cross-linking zones and also dissociate the bundles to widen the pores and allow molecules to enter. Overall, the model of the nuclear pore complex gating shows that the periphery of the NPC central channel consists of a few brushes with many cross-linked bundles due to the tethering of nups. However, the central regions shows a sieve-like structure of bundles with repeated cross-links as tethering of nups is less prominent.[4]

  1. <pubmed>20421988</pubmed>
  2. <pubmed>24558427</pubmed>
  3. <pubmed>24282617</pubmed>
  4. <pubmed>24626154</pubmed>

2.Select an image related to your selected topic sub-section (this can be from one of the 4 above or from elsewhere). The image should be uploaded (with all the required information: description, reference, copyright and student template) and pasted onto the project page sub-section and onto your own personal page.

Charge as a selection criterion for nuclear transport.png

Charge as a selection criterion for nuclear transport [1]

  1. <pubmed>20421988</pubmed>|PLoS One.

© 2010 Colwell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--Z3418837 (talk) 05:34, 3 April 2014 (EST)

Research Articles

--Z3377989 (talk) 12:32, 3 April 2014 (EST)

Nuclear Pore Complexes are formed of many different nucleoporin proteins, roughly estimated to be around 30~ different types. The article focuses on Phenylalanine-Glycine Rich Nucleoporins, otherwise known as FG-nups. FG-nups have what are known as FG motifs, which are repeated sequences of Phenylalanine and Glycine within their Amino Acids. These are most prominent around the central complex and are suggested to contribute to bidirectional transport of large proteins and molecules. By having Transport Factors (TF) attach themselves to these large molecules, the TFs have FG-nup binding sites to allow for transport through the Nuclear Membrane by “widening” the hole to allow for larger structures to pass through. In this article, the researchers were to trying to understand the structure of the nuclear pore complex and how frequent FG-nups can be found within this central zone.[1]

Nuclear Pore[1]

Importin-8 (IPO-8) is part of the Karyopherin β family which govern mostly in nucleocytoplasmic transport of large molecules. One of their major functions is mediation between the nucleoplasm and cytoplasm and the large molecules that reside in either space. In this article, Yao Wei et al focused on IPO-8 and its major function in miRNA transport from the cytoplasm to the nucleus. They found out that during IPO-8 Knockdown, mature miRNAs, although they didn’t decrease in cellular amount, they were not transferred to the nucleoplasm due to IPO-8 being essentially “blocked”. Also, they found out that another complex known as Ago2 was needed to bind with IPO-8 in order to transfer miRNA into the nucleus, although the mechanism is still unclear on how Ago2 binds to miRNA. They used Trypaflavine (TPF) as a variable to disrupt the binding of Ago2 and miRNA, and was shown that IPO-8 still binded to Ago2 and transferred the complex into the nucleoplasm.[2]

FG-nups are assembled in an eight-folded symmetry, also as mentioned above in the previous article, they have repeat motifs of Phenylalanine and Glycine and come in various forms of nucleotide sequencing. Nuclear Localisation Signals may in fact be another form of a transport factor, and is involved in many different models that entail structure of the Nuclear Pore Complex. Mincer and Simon try to create a 3D model depicting the Nuclear Pore Complex without having any connections to any one particular model that has been proposed. FG-nups are single filament that can vary in size, because of this Mincer and Simon try to employ random variations to their model to simulate random FG-FG binding between FG-nups. Another factor involved in nucleocytoplasmic transport is RanGTP which was essentially shown to speed up the transport rate of molecules with Nuclear Localisation Signals. This essentially coincides with the Brownian Ratchet Model, which is the movement of cargo through the NPC through thermal fluctuations. It was previously thought that Transport Factors carrying cargo through the NPC do not get released into the nucleoplasm until it is released by RanGTP. [3]

Transportin molecules were used in this experiment and showed that there was a level of avidity for transport receptors on the Nuclear Transport Receptor- cargo complex to bind with FG-nups on the cytoplasmic side of the NPC and this helped in efficient transportation of the cargo towards the nucleoplasm. It is believed that although NTR helps in membrane permeability, that RanGTP is the factor that releases the cargo into the nucleus and re-use the NTR in the cytoplasm. Each transportin molecule on the bound cargo (M9-βGal‐8C) connects to an FG but is dependent on the availability and density of FG binding sites on the NPC. By understanding structure of FG-nups, they were able to determine that FG-FG binding sites allow for modulation of bidirectional transport and NTR-FG interactions. [4]

  1. 1.0 1.1 <pubmed>24626154</pubmed>
  2. <pubmed>24596094</pubmed>
  3. <pubmed>21690354</pubmed>
  4. <pubmed>24213245</pubmed>

Research Articles and Image

I went for a search after old articles that wrote about Nuclear Pore Complex (NPC) so I could grasp some simple concepts about it. “Architecture and Design of Nuclear Pore Complex” talks about its structure and they figured the approximate diameter of the nuclear pore by coating cargo-receptor with gold particles. Division of the nuclear pore into Peripheral and Central channels was also noticed by observing dissected macronuclei from Xenopus laevis oocytes on electron microscopy. In addition, the article tells you about the role these channels play in passive and active transports through nuclear membrane, as well as a picture of their structure.[1]

This article explore the wide role of Nuclear Pore Complex (NPC) on passive and facilitated transports, once this is the only route material can go from nucleus to cytoplasm and vice-versa. The experiment used HeLa cells, where marked molecules were injected. The range of molecules included ones that could go through NPC either by passive diffusion or receptor-mediated routes. It was shown that ions, metabolites and intermediated-sized macromolecules crossed the nuclear membrane by diffusion, whereas proteins, RNA and ribonucleoprotein complexes needed the facilitated transport. It was noticed that though both transports occurred in the central part of NPC they didn't interfere with each other. However, molecules utilizing the same mode of transport affected each other pathways. Hence it was concluded that passive and facilitated transports don't share the same route.[2]

This article investigates the impact of hormones on nuclear permeability. The experiment was made with hepatic cells and several marked molecules were injected in it. It was observed that Ca+ plays an important role when it comes to increase nuclear permeability. They linked this information to the fact that some hormones, such as vasopressin and angiotensin, increase the amount of Ca+ within the nucleus, therefore they concluded that hormones may have a short-term control over the permeability of nucleus membrane.[3]

This interesting article compares the traffic of molecules in health and disease, such as tumour and viral infections. It mentions oncoproteins and tumour suppressor genes and how their balance within the nucleus is important to keep a normal function of the cell, once these genes regulate cell growth and DNA division. Another important point is the role of Nucleuporine 98 (Nup98) and its relation with disease when affected by mutations. Regarding to viral infections, it’s shown that virus can take over export machineries and hinder mRNA from going to cytoplasm and explains why this is beneficial to the virus.[4]

  1. <pubmed>1617726</pubmed>
  2. <pubmed>17164246</pubmed>
  3. <pubmed>17158097</pubmed>
  4. <pubmed>24530809</pubmed>

Structures of Caldedrin and Jacob.png

Calderin and Jacob, proteins involved in nucleus signaling[1]

  1. <pubmed>18303947</pubmed>|PLOS Biology.

--Z5011434 (talk) 15:08, 3 April 2014 (EST)

Project Contribution

Nuclear Envelope, Importins/Exportins and Disease sections were under my responsibility. I could make readings and finish a draft of two of the sections but couldn't finish my text for Importins/Exportins, wich I will be done by the weekend and then upload it here.

z3377989 Contributions

I have written the first draft for everything under the nucleoporin sub-heading and have added an image to it. I have also written somethings about RanGTP and RanGDP with another image and have referenced all of my work so far. --Z3377989 (talk) 11:10, 1 May 2014 (EST)


Introduction + Complexes

• Images describing the structure of the transport proteins, models and nuclear envelope would be useful

• Abbreviations should be written out in full first otherwise readers won't be clear on what the abbreviations mean, for example 'FG-Nups' - underneath nuclear pore complex models. There was an explanation to what FG-Nups were further down in the project, but it would’ve been more useful if the readers knew what FG-Nups were, before reading about it in nuclear pore complexes

• Definition, structure and function of RanGTP and RanGDP aren't very clear

Quite a few empty headings that need to be filled out

• If possible, expand more on the diseases relating to the Nup nuclear porins, i.e. specific details

• Also, formation of images underneath the image heading should be aligned and fixed

References: some of the references doubled up in the reference list. There should be a link on the side that helps with editing and adjusting the references so that it doesn't double up

Overall, the project has a good basic format and brief introduction to the topic. It can be improved with the addition of more detailed and specific information relating to structure and function and also images to aid with description.

--- --Z3420257 (talk) 06:55, 15 May 2014 (EST)

There is a lot of work still to be done with the page. I think there could be a better way to make the project flow a bit better. Maybe you could do this by doing a brief introduction to a subtopic. You ave included links, which is good. Photos and videos are also included. I think anything visual is very beneficial to a page as it is easier to look at for a person who is still doing basic research and just skimming through the page for the first time. It also help capture the reader attention. I think what could be done though is to move the relevant photos to the topics they are associated to. One thing I would suggest to get done soon would be your introduction and history. These could be a good source of your flow of information.

In the body, I think you can also add more current/future research topics and disease topics. They are very easy to find and tend to be very interesting as I reckon your topic would have a lot to do with genetic defects, considering it is transportation out of the nucleus. One good tip I got from another group was to add the glossary at the end. I think this is good help to the reader. Overall, a bit more research maybe and just improving the flow would really help improve your page.


Group 3: -I think images would be useful in describing pathway the mechanisms involved. -The names should be stated before the names are written in shorthand, so that the reader can know the full name. The information on them is good though. -More information needed on the structure and function of the Rans mentioned. -More headings needed. -Expand the diseases, go into a bit more detail. -With the referencing, need to fix up the list a little bit. There are some which appear twice on the list, so a quick edit will do the job. -I think, overall this project has good information, which needs to be expanded upon and the use of images would really enhance the page.

Group 3 Peer-Review --Z3399239 (talk) 14:31, 15 May 2014 (EST)

Nuclear Envelope: Referencing not complete yet and a very general overview of the topic. Lacks diagrams. Looks like its still a work in progress at this point. Some of the sentence structure does not flow well e.g. "The outer membrane faces the cytoplasm and is continuous and closely associated with the rough endoplasmic reticulum and has ribosomes attached to it.".

Nuclear Pore Complex (NPC): Good referencing. Well structured. Could use some diagrams. Explanation of what "FG-Nups" are (which comes later) at this point.

Nucleoporins: Good introduction to nucleoporins. FG-Nups section is well referenced and provides a good insight into the topic.

RanGTP and RanGDP: Well referenced. Good information. Diagram is useful and accessible.

Nuclear Transport Receptors: Well referenced. Good information.

Overall: Certain sections are well put together e.g. RanGTP and RanGDP, but many parts are still missing. There are some useful diagrams but more could be used to help illustrate concepts. Referencing varies throughout the project but in general is good. At this point the project shows that some key concepts are understood but there are some that still need to be researched and added to. Relatively accessible information that goes beyond lecture material. Glossary could be useful?