Toll like receptors in Chronic Lymphocytic Leukaemia

Literature Review

FILE

T IME SUBMIT T ED

SUBMISSION ID

- The role and importance of autophagy in carcinogenesis

Autophagy is a survival mechanism used by ceHs duri.ng times of nutrient stress, for example, the absence of amino acids,. nitrogen and/or carbon. Lysosomal degradation of organelles and protein aggregates generates energy for the cell in order for i t to survive, as wellll as limiting the cellll's ability to produce toxic substances such as reactive oxidative species (ROS), for example, hydrogen peroxide. Ros£m damage DNA, effectin • A replication and protein synthesis. Eventually, this can lead to carcinogenesis. :A.atophagy has a paradoxical effect, where it can induce carcinogenesis in normal celllls, but within adv:am:ed cancerous cells. it assiis.ts with the survival of the tumour. Over recent years a lot of cancer therapies have been trialled and developed, based O'IT.IM•"'�""'iting autophagic regulators (proteins). However, we still remain unawa ' ut the exact mechanisms of regulators such as b . - /. In normal cells, autophagy pllays an iimportant role in recycling damaged organelles and dysfonctional proteins for energy usage in order to maintain the cell's integrity. This survival mechanism is not limited to the removal of injurious substances from the cell, but it also plays a part in promoting cell senesce,nce. T ui der normal conditions, autophagy is a key component in the prevention of c _[ genesis (Glick et al, 2010). My research question pertains to the role of the B eclin-1 protein in carcinogenesis, a protein which induces autophagy. Therefore, this literature review intends to analyse the current .literature on autophagy in cancer, our current understanding of autophagy, how the analysed literature relates to my research

•question and how we can progress with the current literature we have. The review will include, but not be exclus,ive to Beclin-1. Instead it will look at the relationship between autophagy and carcinogenesis on a wider scope, allowing me to evaluate more liteLatu . Eventually, coming to a conclusion as to why I have chosen to use Beclin- In research question, how the field can progress and how promising the � current state of research is. liafll

There are three type s of autophagy, macro-autophagy, micro-autophagy and chaperone-mediated a utophagy. Macro-autophagy is essentially the rem ova I of structures, not necessarily organelles, but also aggregated proteins for example, which may have lost their functionality. The structures are encased in a double- membrane vesicle known as an autophagosome. This autophagosome will transport the contents to a destructive lysosome, where the constituents can be used to synthesise more protein or used as an energy source (Boya et al, 2013). In micro­ autophagy, th e damaged/dysfunctional contents of the cell are directly taken up by the lysosome via invagination (Glick et al, 2010). Finailly, in chaperone-mediated autophagy the structures are transported to the lysosome by chaperone proteins, which are then translocated iinto the lysosome. These chaperone proteins are granted entry into the lysosome due to the presence of llysosome associated membrane proteins (LAM Ps ). Deficiency of these proteins means the structures can not be trans!ocated into the lysosome (Huynh et al, 2007). Perhaps a deficiency in these proteins contributes to carcinogenesis? Research into the deficiency of

QM

FINAL GRADE

54/0 Literature Review GRADEMARK REPORT

GENERAL COMMENTS

Instructor Do ne well: Yo u have demo nstrated enthusiasm f o r the to pic and been able to identif y so me key, relevant primary so urces and reviews. Yo u have attempted to intro duce a high pro po rtio n o f discussio n into the review.

Fo r impro vement: Overall, the review required a systematic intro ductio n o f key f actual material o n which discussio n co uld be based. T here was an episo dic structure that made it so metimes dif f icult to f o llo w yo ur reaso ning. Pay attentio n to my co mments in the text

Abstract: 0/5 Review: 24 /4 0 Ref erencing: 3/5

PAGE 1

Comment 1 | Present at ion Yo u were instructed to begin yo ur literature review with an abstract. T his is missing f ro m the submissio n.

Having read the paragraph and no ted the lack o f ref erences, yo u may have intended this to be an abstract. Witho ut a title o r heading, this is in f act the beginning o f yo ur review. See my co mment belo w.

Comment 2 ins: may

A/E Af f ect/Ef f ect: T he verb "af f ect" means "to inf luence o r pro duce an ef f ect o n." As a no un "ef f ect" is a result. As a verb "ef f ect" means "to bring into existence." While in mo st cases, an ef f ect is the result o f all that has been do ne to af f ect a situatio n, it is po ssible f o r o ne perso n to ef f ect change.

Strikethrough.

Comment 4

QM

QM

o n

Comment 5 A very vague sentence intro ducing a number o f so f ar unexplo red co ncepts. Otherwise an adequate intro ducto ry passage marred by the co mplete absence o f ref erences. T his latter po int suggests that yo u co nsider this to be an abstract. I suggest that yo u read so me article abstracts caref ully to see ho w they are co nstructed.

Comment 6 T here is insuf f icient inf o rmatio n presented here f o r this co nclusio n to be drawn.

Tick (T ick)

Strikethrough.

Comment 8 Vague. T here must be a purpo se to this wider review. What questio n are yo u seeking to address? What are the bo undaries f o r yo ur review?

Comment 9 Go o d to include a statement o f intent, but do es need to be precise and co ncise.

PAGE 2

Citation required Yo u have no t ref erenced the so urce o f this inf o rmatio n. Fo r advice o n ref erencing, please go to http://www.westminster.ac.uk/library- and- it/suppo rt- and- study- skills/guides- and- tuto rials/ref erencing- yo ur- wo rk

Comment 10 Go o d questio n, but why start discussing limitatio ns to kno wledge here when the three mo dalities have no t been described in any detail? It is no t suf f icient to state that research is "f lawed" witho ut presenting evidence to suppo rt this assertio n.

Comment 11 T his is no t required...

Comment 12 f o r

Comment 13 Do no t use demo tic English in academic writing. A reader f o r who m English is a seco nd o r third language may no t understand the idio m (yeast f issio n o r gro wing trees?)

Comment 14 T here are several co ncepts intro duced into this o ne paragraph. T hese sho uld be presented

QM

QM

in separate paragraphs f o r clarity (unless they are being co mpared directly)

Comment 15 Yo u need to present evidence f o r this. Yo u have to reveal the gaps in kno wledge bef o re making such a statement.

Comment 16 Do no t co ntract wo rds in f o rmal writing. Go o d to see the enthiusiasm f o r the to pic, but there are to o many "interesting to pics" and to o f ew details o f what these might be...

Comment 17 Date required

Comment 18 Warning: dysplasia is NOT cancer. Please use Weinberg (2014 ) as a co re ref erence to build yo ur kno wledge o f cancer bio lo gy.

Comment 19 Go o d idea f o r discussio n, but yo u need to present (brief ly) the evidence...

Comment 20 Marking will be with a lighter to uch f ro m here, but be aware o f the nature o f the co mments that I have made already

Citation required Yo u have no t ref erenced the so urce o f this inf o rmatio n. Fo r advice o n ref erencing, please go to http://www.westminster.ac.uk/library- and- it/suppo rt- and- study- skills/guides- and- tuto rials/ref erencing- yo ur- wo rk

Comment 21 What is p62 and what do es it do ? Yo u have still to explain the mechanics o f auto phagy

Comment 22 A serio us interpretatio nal erro r here. Yo u will have seen that auto phagy is a pro cess f o und in yeasts, wo rms, mice and humans. T his suggests tremendo us selectio n pressure f o r co nservatio n o f genes and f unctio n.

Conceptual understanding What do es this mean? T here sho uld be a suppo rting explanatio n o r discussio n that demo nstrates yo ur understanding o f the co ncept.

Comment 23 it is no t a PK...but yo u will be lo o king at the distributio n o f the pro tein.

PAGE 3

Comment 24

QM

T here is a great deal mo re in the literature o n the implicatio ns o f BECN1 haplo insuf f iciency f o r cancer risk...

Comment 25 Co ncept issue: yo u need to think abo ut (1) mo dern scientif ic metho do lo gy and the f e# alsif icatio n o f hypo theses and (2) ho w o ne can "pro ve" a negative...

Comment 26 Right idea, but described so minimally as to make little sense.

Comment 27 T his sho uld be a review o f the literature that identif ies with justif icatio n a specif ic research pro blem. T his "internal" co nversatio n is to be had with yo ur superviso r o r peers and sho uld no t be here.

Makes no sense T his do es no t make sense.

PAGE 4

Comment 28 Mo stly waf f le...

Comment 29 An explanatio n is required.

PAGE 5

Comment 30 Ref erences must be listed alphabetically by f irst autho r

PAGE 6

RUBRIC: COURSEWORK FEEDBACK SHEET

RELEVANCE

A

B

C

D

E

F

ANALYSIS

A

B

C

D

E

F

PRESENT ED QUA

A

B

C

D

E

F

QUALIT Y REF

A

B

B

Relevance o f co ntent, depth o f discussio n and demo nstratio n o f understanding

First Class Ho no urs. (>7 0%)

Upper Seco nd Class Ho no urs. (60- 69%)

Lo wer Seco nd Class Ho no urs. (50- 59%)

T hird class Ho no urs. (4 0- 4 9%)

Fail. (30- 39%)

Fail. (<30%)

C

Analysis and evaluatio n o f ref erence material

First Class Ho no urs. (>7 0%)

Upper Seco nd Class Ho no urs. (60- 69%)

Lo wer Seco nd Class Ho no urs. (50- 59%)

T hird class Ho no urs. (4 0- 4 9%)

Fail. (30- 39%)

Fail. (<30%)

C

Quality and co herence o f arguments presented

First Class Ho no urs. (>7 0%)

Upper Seco nd Class Ho no urs. (60- 69%)

Lo wer Seco nd Class Ho no urs. (50- 59%)

T hird class Ho no urs. (4 0- 4 9%)

Fail. (30- 39%)

Fail. (<30%)

C

Quality o f ref erence so urces selected and co rrect citatio n o f tho se ref erences

First Class Ho no urs. (>7 0%)

Upper Seco nd Class Ho no urs. (60- 69%)

C

D

E

F

PRESENT AT ION

A

B

C

D

E

F

Lo wer Seco nd Class Ho no urs. (50- 59%)

T hird class Ho no urs. (4 0- 4 9%)

Fail. (30- 39%)

Fail. (<30%)

C

Length o f submissio n, written style, o rganisatio n and presentatio n

First Class Ho no urs. (>7 0%)

Upper Seco nd Class Ho no urs. (60- 69%)

Lo wer Seco nd Class Ho no urs. (50- 59%)

T hird class Ho no urs. (4 0- 4 9%)

Fail. (30- 39%)

Fail. (<30%)