Giant Jamboree 2014 , Hynes Convention Center, Boston MA iGEM Team of - - PowerPoint PPT Presentation

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Giant Jamboree 2014 , Hynes Convention Center, Boston MA iGEM Team of - - PowerPoint PPT Presentation

Giant Jamboree 2014 , Hynes Convention Center, Boston MA iGEM Team of Ben-Gurion University, Be'er-Sheva, Israel The e Met etaboli bolic c Syndrom drome Intro The Metabolic Syndrome What is it? Current treatment High Goals Diabetes


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Giant Jamboree 2014, Hynes Convention Center, Boston MA iGEM Team of Ben-Gurion University, Be'er-Sheva, Israel

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The e Met etaboli bolic c Syndrom drome

High Plasma Triglycerides Low HDL (good) Cholesterol Fatty liver Hyperglycemia Diabetes Type 2 High blood pressure Insulin resistance Abdominal Obesity

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

What is it? Current treatment

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Health thy y lifest estyle yle:

  • Appropriate dietary
  • Routine exercise
  • Well sleeping

Lower risk for Metabolic Syndrome

Some e Facts

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

What is it? Current treatment

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  • Sweet beverages
  • High-fat food
  • Not enough exercising

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

What is it? Current treatment

34 34% 60 60%

Quick Quiz

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Healthy lifestyle

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

What is it? Current treatment

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  • Treating the symptoms rather

than the causing factors

  • Inefficient overall treatment
  • Conflicting side effects

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

What is it? Current Treatme ment

Curre rrent nt Treatmen eatment

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Less people suffering from the metabolic syndrome

Goal als:

1) Create synergetic multifunctional treatment 2) Raise awareness in population at risk

Intro

Goals ls

Strategies Policy & Practices

The

Metabolic Syndrome

The e Vision

  • n
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  • Prof. Jaco

cob Bar-Ta Tana, MD Metabolic Syndrome expert

  • Prof . Assaf

af Rudi udich ch, MD Endocrinologist, Diabetes expert

Intro

Goals ls

Strategies Policy & Practices

The

Metabolic Syndrome

Amon

  • ng

g Our Con

  • nsultan

sultants ts

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Fatty acid accumulation in the liver Insulin resistance

The e Target rget Elem ements ts

Intro

Goals ls

Strategies Policy & Practices

The

Metabolic Syndrome

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Fatty acid accumulation in the liver Insulin resistance

“Aspiration Shift” “Intelligent Medication” “Artificial Exercise”

1 2 3

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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  • Non–adipose fat accumulation
  • Fatty liver is highly correlated

with the Metabolic Syndrome

  • We will treat Fatty Liver!

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Fatty ty Liver

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“Artificial Exercise”

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication

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DNP - 1930’s dietary aid:

“Artificial Exercise”

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication

  • Uncoupling factor
  • Increasing oxidative

phosphorylation

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“Artificial Exercise”

DNP - 1930’s dietary aid:

  • Effective

for losing weight

  • Side effect –

heating production

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication

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Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication

Me Mechani nism sm

“Artificial Exercise”

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pcDNA3.1 UCP UCP1 Normal al HepG2

No stain 10 nM TMRM 25 nM TMRM 10 nM TMRM 25 nM TMRM

HepG2 - Human Hepatocarcinoma cell line

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artif ific icia ial l Exercis ise Aspiration Shift Intelligent Medication

Res esults ts

“Artificial Exercise”

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Indi dire rect ctly increasing

  • f fatty acid oxidation
  • Encouraging lipid transport
  • Mitochondrial biogenesis

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspira iratio ion Shift Intelligent Medication

Stop p storing ing and d start rt burning! ing!

“Aspiration Shift”

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Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspira iratio ion Shift Intelligent Medication

Me Mechani nism sm

“Aspiration Shift”

Fatty acid

  • xidation
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Goal:

Validating the pers rson

  • naliz

alized ed behavior

  • f the treatment

Methods ds & T Tools

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspira iratio ion Shift Intelligent Medication

Mo Modeling ling

“Aspiration Shift”

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The model predicts:

“Aspiration Shift” is a self-regulating personalized treatment

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspira iratio ion Shift Intelligent Medication

Model del Resul sults ts

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Insulin Glucose absorption Insulin resistance Insulin resistance in the liver Glucose absorption Hyperglycemia

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion

Insuli lin n Resist stance ance

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Current nt treatmen tment: t:

  • High dose injection of insulin

Disadva vant ntages:

  • Inefficient
  • Uncontrolled
  • Non-specific

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion

“Intelligent Medication”

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Targeted Delivery?

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion

Me Mechani nism sm

“Intelligent Medication”

Based on “Conditional Dicer Substrate Formation via Shape and Sequence Transduction with Small Conditional RNAs” (Hochrein, Schwarzkopf, Shahgholi, Yin, & Pierce, 2013)

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OFF state ON state

Produced by Nupack.org

scRNA NA Constru tructo ctor

“Intelligent Medication”

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion

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eGFP eGFP+mRuby2 mRuby2

Trigger Gene: mRuby2 Silencing Target Gene: eGFP FP

Pr Proof f of C f Concept ept

“Intelligent Medication”

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion

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Our specially designed hairpin reduced the expression of eGFP by 56

56%!

Pr Proof f of C f Concept ept

“Intelligent Medication”

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Artificial Exercise Aspiration Shift Intell llig igent Medi dicatio ion

44.4 38.2 0.0 20.0 40.0 60.0 80.0 100.0 scRNA hairpin siRNA positive control mRNA express ssion ion levels ls (vs. untreate ted cells) s)

eGFP mRNA expre ression profi file

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“Artificial Exercise”

  • Evaluation of UCP1 functionality

“Aspiration Shift”

  • Mathematical verification of the personalized

behavior

“Intelligent Medication”

  • scRNA constructor software
  • Verification of the scRNA hairpin functionality

Intro

Goals

Strategies Policy & Practices

The

Metabolic Syndrome

Mu Multicom compl plexit exity Treatment ment

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Policy & Practices Research

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CEO of the Israeli Diabetes Association

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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The Bedou

  • uin

ins

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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  • Dr. Younes

Abu Rabia, MD

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

The Bedou

  • uin

in Campaign gn

1) Raise awareness 2) Increase prevention behaviors 3) Spread the vision of synthetic biology treatment

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קילובטמ רודסבמא(הנומת )עוריאהמ

  • הרטמ: ליצהל תטיקנו תועדומ תאלעה ידי לע םייח

הלועפ

  • םימדקתמ םילופיטל עקרקה תא חינהל
  • ירפסמ רואית– תופתתשה40 םיטנדוטס

ו האופרה תועוצקממ5 םיעצוקמ םירבוד

Aims:

  • Raising awareness
  • Set the ground for advanced therapy

Achievements:

  • 40 students participation
  • 5 professional speakers

supporting the idea

  • Participation and

honor certificates

Metab tabolic lic Amb mbas assadors sadors

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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תוגלמ תחקל תוגלמ איבמ רוטקוד רניא לש הנומת ןורילמ

  • Bedouin student will

establish a new branch

  • f the Israeli Diabetes

Association in Rahat

  • 8 Bedouin students will

volunteer in diabetes clinics of their communities

Scholar

  • larsh

ship ips

up to 70

70% tuition

  • n!

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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  • םדקומ יוליגו אירב לושיב תנדס (הנומת)
  • הרטמ
  • ירפסמ רואית25 תויאודב םישנ
  • םישנל תומדקומ סוקולג תוקידב

Aims:

  • Impact community’s nutritious habits
  • Create a strong link between the Diabetes clinic in Rahat

and the Israeli Diabetes Association

Achievements:

  • 25 Bedouin women participation
  • Glucose level monitoring for the participants
  • Sharing tips for healthier cooking and consuming
  • Established a repeating annual event

Heal alth thy y Cooki king ng Works rksho hop p

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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  • קניטה לש הנומתו תואירבה תרש םע הנומת

ןבל םחל עקרבו םיקוח לש רפס קיזחמ רוטקוד הקותמ תנמשו

Ne Network rkin ing g

  • Israeli Minister of Health, Mrs. Yael German
  • Mayor of Be'er-Sheva
  • Ben-Gurion University President
  • CEO of the Israeli Diabetes Association
  • CEO of Trigger Foresight (Deloitte)
  • Public figures
  • Doctors
  • Metabolic Syndrome experts

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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  • Inner Doctor video reached over

50,000 impression

  • ns
  • 3600 likes on our Facebook page
  • E-Mails and messages from people all over the

world looking forward to use our Inner Doctor technology

Inner Docto tor Impact ct

Intro Goals

Strategies Policy & Practices

The

Metabolic Syndrome

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Ac Acknowledg ledgeme ements nts

  • Prof. Smadar Cohen
  • Dr. Efrat Forti
  • Dr. Emil Rubinov

Ms.Dana Neeman

  • Prof. Assaf Rudich
  • Prof. Iris Shai
  • Prof. Emeritus Jacob Bar-Tana
  • Prof. Ariel Kushmaro
  • Dr. Ilana Harman

Ms.Karin Yaniv

  • Prof. Ariel B. Lindner
  • Dr. Omri Amirav-Drori
  • Dr. Olga Kryukov
  • Prof. Varda Shoshan-Barmatz

Mr.Matan Goldshtein

  • Mr. Alon Szczupak
  • Mr. Edan Elovic
  • All custom DNA was synthesized by GeneScript

(HSP70, UCP1, DsbA-L, AdipoQ)

  • pcDNA3 mRuby2 was supplied by Addgene
  • All custom RNA was synthesized by IDT

(scRNA parts A and B)

Want to hear more? come meet us at

poster r #26 26

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