PLASMA POSTER COMPETITION

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PLASMA POSTER COMPETITION. All Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster. Mitochondrial DNA?. Western Blots?. Bladders?. . Prostates?. . Urine?. . Non-invasive assessment of bladder function. Jennifer Caffarel. - PowerPoint PPT Presentation

Text of PLASMA POSTER COMPETITION

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • Jennifer Caffarel

  • 1/3 of menwill havebothersome urinary symptomsat some point in their life

  • then you might have

    Bladder Outlet Obstruction

  • The prostate gland surrounds the urethraWith increasing age, it increases in size and can obstruct the urethra

  • Urine flow can be quantified by a technique called uroflowmetry. and can cause a slow or weak urine flow.

  • Uroflowmetry is performed in clinics, using expensive electronic flowmetersAttending a flow clinic can be a long and tedious experience

  • and having to fill and empty your bladder several times in a short period of time is rather unnatural!

  • The data obtained from flow clinics is variable, due to a number of factors:

    Time of day Volume of urine in the bladder Emotional state of patient

  • The aim is to improve the diagnosis made using uroflowmetry.For example, we tested a very basic flowmeter, to obtain more representative results.vs.Basic FlowmeterElectronic Flowmeter

  • This is how the basic flowmeter is used: The patient takes the device home Makes multiple measurements over several days, in his own time

  • This home flowmeter provided more representative results than in-clinic flows. And 2 patients who could not urinate in the clinic were able to use this device.

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • Questions (and some answers) on research into stomach cancerClaire Worrall

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  • WhoIt is difficult to predict.

    It depends on:

    If you have H. pylori infectionWhat you eatIf you have stomach ulcersHow much alcohol you drinkIf you smokeYour Body Mass IndexWhat country you live inYour genetic backgroundYour gendergets stomach cancer?

    So biological markers of early disease would be very useful.

  • Whatchanges occur in stomach cancer?Expression levels of many proteins are altered

    We are studying one protein whose expression is lost in the majority of stomach cancers:

    TFIZ1 is expressed in mucin-secreting cells and secreted into the mucous layer in the stomach.

    It is virtually undetectable by RT-PCR in our panel of 7 gastric cancer cell lines.

  • Wherecan we study stomach cancer?

    These behaviours in patient cancer cells help determine tumour growth and the ability to metastasize.There is limited supply of patient samples.

    However, we can grow stomach cancer cells in the lab to perform tests on.

    These cells grow and divide, allowing us to measure the effects of different conditions on:How fast they grow and divideHow easily they dieHow quickly they move

  • Whendo we study a protein in stomach cancer?

    When we have evidence linking it to stomach cancerTFIZ1 is bound in the stomach to TFF1, which has many links to cancer:High expressionin oestrogen responsivebreast cancer

  • Howare we studying this protein?By introducing controllable TFIZ1 expression into stomach cancer cells:pTet-OffneoRtTAtTAneoRTRE TFIZ1pTRE-Tight TFIZ1TFIZ1TRETFIZ1OffTFIZ1On1. Transfect inregulator plasmid2. Transfect inTFIZ1 plasmidStomach cancerCell lineAddingdoxycyclineturns off TFIZ1expressionThe cells nowexpress TFIZ1

  • Whydo we study a protein in gastric cancer?If we know

    WHY the expression changesWHAT the protein doesIn the normal stomachIn stomach cancer WHEN the expression changes

    It can

    Help us decide whether it might be a good early indicator of cancer.

    Help us decide whether it might be a good therapeutic target.

  • Acknowledgements: Felicity May Herbie Newell Northern Institute for Cancer Research

    Claire Worrallclaire.worrall@ncl.ac.uk

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • Forkhead Proteins & CancerFrances PurtilliCAMB

  • Forkhead Proteins & CancerUnregulated cell proliferation is a characteristic of all cancersUnderstanding the mechanisms behind cell proliferation will help in the treatment and prevention of cancer

  • Forkhead Proteins & CancerMG2G1SM Phase (Mitosis)Replicated DNA is equally distributed into 2 cellsCell proliferation is controlled by a series of events known as the Cell Cycle12The cell cycle consists of 4 phases:

    G1 and G2 are gap phases which prepare the cell for its next step3 & 4 Genetic material is copied and 2 identical cells are formed S PhaseDNA is replicated

  • Forkhead Proteins & CancerForkhead Transcription Factors (FKH-TF) are critical for the regulation of the cell cycle

    TARGET GENEGENE SWITCHED ONFKH-TFForkhead proteins have been associated with various human cancersThey bind upstream of genes involved in mitosis, and activate their expression

  • Forkhead Proteins & CancerForkhead proteins are vital for mitosis in all eukaryotes, from yeast to man

    Yeast is easy to manipulate, genetically and biochemically

    Therefore it is a valuable model to study forkhead proteins, and improve our knowledge of the cell cycle in humansIn the future, this knowledge could potentially be used to improve existing cancer therapies

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • The Development of Small Molecule Inhibitors of the MDM2-p53 Interaction Junfeng Liu

  • p53 is a Tumour Suppressorp53+/+p53+/-p53-/-1% at 18 months% mice with tumour74% at 6 months2% at 9 monthsDonehower et al. Nature, 1992Also suggest to read Donehower et al. Nature genetics, 1993

  • MDM2 controls p53 through an auto- regulatory negative-feedback loop p53MDM2 mdm2 mRNA mRNA of other targetsThree mechanism to repress p53 by activation of MDM2-expression:MDM2 binds p53 at transactivation domain and blocks its ability to activate transcriptionMDM2 acts as an E3 ubiquitin ligase that promotes p53s proteasomal degradationMDM2 is involved in the nuclear export of p53

  • Breaking the negative-feedback loop with antagonists Therapeutic potential Rescue of p53 Function by Disrupting the p53MDM2 Interaction. Blocking MDM2 Expression Inhibiting MDM2 Ubiquitin Ligase Activity Disruption of the p53MDM2 bindingp53p53MDM2MDM2 mdm2 mRNA mRNA of other targets p53s proteasomal degradation

  • Possible MethodsDisruption of the p53MDM2 Binding Interaction Antibody microinjectionPeptide analogues corresponding to the MDM2 binding domain of p53Small molecular weight compounds

  • The p53-MDM2 interaction: Unique binding site

    Unique& Good for Small Molecule Drug Design and Development

  • MDM2 protein and p53 peptide structures come from Protein Data Bank.PyMOL Software were applied for the followed cartoons.Structure based drug designMDM2 Binding Domain(Binding area high lighted)

  • Structure based drug design8mer p53 peptide Binding with MDM2

  • Structure based drug designThree key residues of p53 in the hydrophobic pocket of MDM2

  • Structure based drug designThree key residues of p53 were picked out for drug design

  • Structure based drug designDrug design based on the three key residues of p53

  • Structure based drug designDesigned small molecule scaffold

  • Structure based drug designManual docking of the compound with MDM2 binding domain

  • Inhibitor Screen Using ELISA

  • Cellular activity Confirmation via Western Blotting AssayEffect of MDM2 inhibitors on the cellular levels of p53, MDM2 and p21Nutlin-3NU8XXXMDM2p53p21ActinDMSO 0.5 1 10 1 10 20 mM

  • Thank you for your attention!

  • PLASMA POSTER COMPETITIONAll Staff and Students are invited to use the ballot papers below to vote for your favourite plasma poster

  • and tools to diagnose Lower Urinary Tract Dysfunction

  • having to go in the middle of the nightinability to pass any water1 in 3 men will suffer urinary symptoms in their life:

    struggling to begin peeinghaving to rush to the toilethaving to go oftenpain while peeingPoor streamTerminal dribbleIncontinenceIncomplete emptying

  • To diagnose the cause we need to measure:Bladder pressureUrine flow rateVolume of urine voided among other tests

  • How do you take a bladder pressure measurement?Well, how do you take a blood pressure measurement?Use the same principle

  • and measure the pressure to stop urine flow!Place a small, inflatable cuff around the penisPressureFlow rateVolumeFlow is interruptedPressure is measured

  • Penile Cuff MachineWe can also use it to measure the bladder characteristics in healthy people to further understand the mechanics of the lower urinary tract. Conventionally, pressure- flow measurements would require urethral catheterisation, an uncomfortable procedure with risk of infection.We can now use this non-invasive machine clinically to diagnose Bladder Outlet Obstruction in patients.

  • With this tool we hope to:Verify theoretical bladder modelsUnderstand better how t