Difference between revisions of "User:Sarah.Minucci"

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==Research Topic==
 
==Research Topic==
 
'''Mentor: Dr. Stephen Merrill''' <br>
 
'''Mentor: Dr. Stephen Merrill''' <br>
 +
'''Working title: The relationship between leptin and inflammation determines critical points in excess nutrition''' <br>
 
<br>
 
<br>
I will be researching the influence of leptin in the body, especially regarding fat, inflammation and immunity.  Leptin, a hormone secreted by fat and fatty tissue which has pro-inflammatory effects in the body, provides a link between nutritional intake and the immune system.  Much is still unknown about these connections, and my goal is to create a mathematical model of some aspect of leptin's influence in the body.
 
  
 +
'''Abstract:''' Research shows a significant relationship between leptin, a hormone involved in energy intake and expenditure, and inflammation in adipose tissue, the main depot of fat storage. These findings suggest an important factor in the drastic weight increase associated with obesity: a cycle of inflammation due to increases in leptin levels.  This inflammation and subsequent weight gain, as well as difficulty in losing weight, could help to explain why lifestyle changes are often not enough to mediate obesity or keep weight off long-term.  The pleiotropic role of leptin not only points to its influence in obesity, but also its comorbidities, including type 2 diabetes mellitus, metabolic syndrome, and heart disease, as well as in general immune system dysfunction.  In fact, leptin seems to be a crucial factor in the prevalence of autoimmune diseases in women, especially women with greater amounts of adipose tissue.  Through construction of a mathematical model of the relationships between leptin, inflammation, and adipose tissue, we can better understand the role of leptin in adipose tissue inflammation, specifically in women.  Insight into these relationships is necessary in better treating obesity, understanding the sexual dimorphism of immune system dysfunction, and determining risk for autoimmune diseases and obesity-related health complications.
 +
<br>
 +
<br>
 
==Milestones & Goals==
 
==Milestones & Goals==
 
===Week 1===
 
===Week 1===
Line 20: Line 23:
 
*3-4 pages of research paper
 
*3-4 pages of research paper
 
*Key research topics:
 
*Key research topics:
***Look for inflammatory molecules that are measured regularly that will help to gauge inflammation levels
+
**Look for inflammatory molecules that are measured regularly that will help to gauge inflammation levels
***A biomarker to quantify inflammation levels
+
**A biomarker to quantify inflammation levels
  
 
===Weeks 5-10===
 
===Weeks 5-10===
Line 30: Line 33:
 
*Thyroid
 
*Thyroid
 
*Sexual dimorphism of leptin levels
 
*Sexual dimorphism of leptin levels
 +
<!--
 +
*Natal
 +
*Breast cancer
 +
-->
  
 
==Research Log==
 
==Research Log==
Line 64: Line 71:
 
*Read articles linking inflammation to leptin (key words: thyroid, TNF, T-cells)
 
*Read articles linking inflammation to leptin (key words: thyroid, TNF, T-cells)
 
'''Thursday'''
 
'''Thursday'''
*Compiled information about leptin/inflammation/immunity
+
*Compiled information and wrote several pages of paper about leptin/inflammation/immunity
 
*Met with Dr. Merrill - threw out linear model and opted to try some kind of quadratic model
 
*Met with Dr. Merrill - threw out linear model and opted to try some kind of quadratic model
 
'''Friday'''
 
'''Friday'''
 
*Organized wiki page
 
*Organized wiki page
<!--
+
*Wrote about findings on leptin, inflammation, and immunity
 +
*Wrote new proposal for mathematical model equations
 +
 
 
===Week 3 / / 6.15-19===
 
===Week 3 / / 6.15-19===
 
'''Monday'''
 
'''Monday'''
*
+
*Finished Friday's paper
 +
*Literature search for biomarkers of inflammation
 +
*Investigated role of estrogen in obesity, breast cancer and the immune system
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Continued investigating biomarkers
 +
*Met with Dr. Merrill
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Focus: quantifying the relationship between fat and inflammation
 +
*Literature on inflammation in fat, sexual dimorphism in fat distribution and leptin levels
 
'''Thursday'''
 
'''Thursday'''
*
+
*Created a visual model of a leptin/inflammation feedback loop (solidified our hypothesis)
 +
*''Responsible Conduct of Research'' training
 
'''Friday'''
 
'''Friday'''
*
+
*Solidified feedback loop
 +
*Met with Dr. Merrill
 +
 
 
===Week 4 / / 6.22-26===
 
===Week 4 / / 6.22-26===
 
'''Monday'''
 
'''Monday'''
*
+
*Played around with equations; fine-tuned
 +
*Research on cytokines
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Continued working on equations
 +
*Met with Dr. Merrill
 +
*Tweaked equations
 +
*Started final paper
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Worked on final paper
 
'''Thursday'''
 
'''Thursday'''
*
+
*Worked on final paper and mid-REU presentation
 
'''Friday'''
 
'''Friday'''
*
+
*Met with Dr. Merrill
 +
*Worked on presentation and final paper
 +
 
 
===Week 5 / / 6.29-7.3===
 
===Week 5 / / 6.29-7.3===
 
'''Monday'''
 
'''Monday'''
*
+
*Worked on presentation
 +
*Literature research on questions about SAT and measures of inflammation:
 +
**In the literature, how is inflammation described/measured?
 +
**How does VAT produce more inflammation than SAT?
 +
**How does TNF-alpha increase adipocyte apoptosis?
 +
 
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Worked on presentation
 +
*Met with Dr. Merrill
 +
*Worked on visual representation of equations
 +
 
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Worked on presentation
 +
*Literature research on sexual dimorphism information and verification
 +
*Visual representation of equations
 +
 
 
'''Thursday'''
 
'''Thursday'''
*
+
*Attended other students' midpoint presentations
 +
*Updated wiki
 +
*Attended graduate student's Master's thesis presentation
 +
 
 
'''Friday'''
 
'''Friday'''
*
+
*OFF (Fourth of July holiday)
 +
 
 
===Week 6 / / 7.6-10===
 
===Week 6 / / 7.6-10===
 
'''Monday'''
 
'''Monday'''
*
+
*Research on nonlinear systems & equilibrium points
 +
*TikZ
 +
*Writing about equations
 +
 
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Writing about equations
 +
*RCR training
 +
*Evaluated L as a function of SAT
 +
 
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Writing about equations
 +
*MATLAB
 +
*Met with Dr. Merrill
 +
 
 
'''Thursday'''
 
'''Thursday'''
*
+
*MATLAB simulations
 +
 
 
'''Friday'''
 
'''Friday'''
*
+
*Updated wiki
 +
*MATLAB simulation
 +
 
 
===Week 7 / / 7.13-17===
 
===Week 7 / / 7.13-17===
 
'''Monday'''
 
'''Monday'''
*
+
*Mathematical analysis of cases of SAT values and their relationships with inflammation and leptin
 +
 
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Analysis of cases
 +
*Writing for final paper
 +
*Read literature about possible applications of the model
 +
 
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Read literature about possible applications of the model
 +
*Met with Dr. Merrill
 +
*Writing about system of equations
 +
*Phase plane analyses of cases
 +
*MATLAB simulations of cases
 +
 
 
'''Thursday'''
 
'''Thursday'''
*
+
*Writing about cases
 +
*MATLAB simulations of cases
 +
 
 
'''Friday'''
 
'''Friday'''
*
+
*Writing about cases
 +
*Writing: motivation, introduction, research goals
 +
 
 
===Week 8 / / 7.20-24===
 
===Week 8 / / 7.20-24===
 
'''Monday'''
 
'''Monday'''
*
+
*Writing final paper
 +
*Reading literature related to potential applications of the model
 +
*Making connections between model and its applications
 +
*MATLAB simulations
 +
 
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Meeting with Dr. Merrill
 +
*Writing final paper
 +
*Reading literature and making connections related to potential applications of the model
 +
*Compiling references
 +
 
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Writing proofs
 +
*Working on poster
 +
 
 
'''Thursday'''
 
'''Thursday'''
*
+
*Writing paper
 +
*Working on poster
 +
 
 
'''Friday'''
 
'''Friday'''
*
+
*Meeting with Dr. Merrill
 +
*Working on poster
 +
 
 
===Week 9 / / 7.27-31===
 
===Week 9 / / 7.27-31===
 
'''Monday'''
 
'''Monday'''
*
+
*Poster
 +
*Paper
 +
 
 
'''Tuesday'''
 
'''Tuesday'''
*
+
*Paper
 +
 
 
'''Wednesday'''
 
'''Wednesday'''
*
+
*Writing paper and formatting it for journal submission
 +
 
 
'''Thursday'''
 
'''Thursday'''
*
+
*Formatting for journal
 +
*Compiling references
 +
 
 
'''Friday'''
 
'''Friday'''
*
+
*Formatting for journal
 +
*Working on presentation
 +
 
 +
<!--
 
===Week 10 / / 8.3-7===
 
===Week 10 / / 8.3-7===
 
'''Monday'''
 
'''Monday'''

Latest revision as of 12:38, 3 August 2015


Research Topic

Mentor: Dr. Stephen Merrill
Working title: The relationship between leptin and inflammation determines critical points in excess nutrition

Abstract: Research shows a significant relationship between leptin, a hormone involved in energy intake and expenditure, and inflammation in adipose tissue, the main depot of fat storage. These findings suggest an important factor in the drastic weight increase associated with obesity: a cycle of inflammation due to increases in leptin levels. This inflammation and subsequent weight gain, as well as difficulty in losing weight, could help to explain why lifestyle changes are often not enough to mediate obesity or keep weight off long-term. The pleiotropic role of leptin not only points to its influence in obesity, but also its comorbidities, including type 2 diabetes mellitus, metabolic syndrome, and heart disease, as well as in general immune system dysfunction. In fact, leptin seems to be a crucial factor in the prevalence of autoimmune diseases in women, especially women with greater amounts of adipose tissue. Through construction of a mathematical model of the relationships between leptin, inflammation, and adipose tissue, we can better understand the role of leptin in adipose tissue inflammation, specifically in women. Insight into these relationships is necessary in better treating obesity, understanding the sexual dimorphism of immune system dysfunction, and determining risk for autoimmune diseases and obesity-related health complications.

Milestones & Goals

Week 1

Verification of leptin production and relation to amount of fat

  • 3-5 pages of research paper
  • Key research topics:
    • What is the relationship between fat and leptin?
    • Is it linear or exponential or something else?
    • What are the units involved?

Weeks 2-5

How are leptin levels related to amount of inflammation?

  • 3-4 pages of research paper
  • Key research topics:
    • Look for inflammatory molecules that are measured regularly that will help to gauge inflammation levels
    • A biomarker to quantify inflammation levels

Weeks 5-10

Choose one of the following directions and develop its relationship with leptin, inflammation & autoimmunity

  • Diabetes
  • Heart Disease
  • Drug-induced autoimmunity
  • Thyroid
  • Sexual dimorphism of leptin levels

Research Log

Week 1 / / 6.1-5

  • Introduction to differential equations
  • Compiled research focus & milestones with Dr. Merrill
  • Became familiar with RefWorks & library resources
  • Became familiar with MatLab
  • Read literature about my topic and found answers to the following questions via databases such as Medline and Web of Science
    • What is the rate of release of adipokines from fat?
    • When leptin is released, where does it go and what is its rate of metabolism?
    • What are the units involved in the metabolism rate?
    • How does leptin relate to fat?
    • Is the leptin-fat model linear?
    • How is leptin measured?
    • Is the leptin-fat relationship related to gender?
  • Investigated free leptin vs. bound leptin

Week 2 / / 6.8-12

Monday

  • Condensed research so far into questions answered
  • Wrote part of research paper
  • Started researching inflammation and leptin

Tuesday

  • Researched bound and free leptin
  • Wrote part of research paper
  • Researched inflammation
  • Found research that may point to an exponential relationship between leptin and fat
  • Met with Dr. Merrill

Wednesday

  • Focuses: BMI, inflammation
  • Verified linear relationship between BMI and weight/fat - this could pose some problems for a linear model of leptin and fat
  • Read articles linking inflammation to leptin (key words: thyroid, TNF, T-cells)

Thursday

  • Compiled information and wrote several pages of paper about leptin/inflammation/immunity
  • Met with Dr. Merrill - threw out linear model and opted to try some kind of quadratic model

Friday

  • Organized wiki page
  • Wrote about findings on leptin, inflammation, and immunity
  • Wrote new proposal for mathematical model equations

Week 3 / / 6.15-19

Monday

  • Finished Friday's paper
  • Literature search for biomarkers of inflammation
  • Investigated role of estrogen in obesity, breast cancer and the immune system

Tuesday

  • Continued investigating biomarkers
  • Met with Dr. Merrill

Wednesday

  • Focus: quantifying the relationship between fat and inflammation
  • Literature on inflammation in fat, sexual dimorphism in fat distribution and leptin levels

Thursday

  • Created a visual model of a leptin/inflammation feedback loop (solidified our hypothesis)
  • Responsible Conduct of Research training

Friday

  • Solidified feedback loop
  • Met with Dr. Merrill

Week 4 / / 6.22-26

Monday

  • Played around with equations; fine-tuned
  • Research on cytokines

Tuesday

  • Continued working on equations
  • Met with Dr. Merrill
  • Tweaked equations
  • Started final paper

Wednesday

  • Worked on final paper

Thursday

  • Worked on final paper and mid-REU presentation

Friday

  • Met with Dr. Merrill
  • Worked on presentation and final paper

Week 5 / / 6.29-7.3

Monday

  • Worked on presentation
  • Literature research on questions about SAT and measures of inflammation:
    • In the literature, how is inflammation described/measured?
    • How does VAT produce more inflammation than SAT?
    • How does TNF-alpha increase adipocyte apoptosis?

Tuesday

  • Worked on presentation
  • Met with Dr. Merrill
  • Worked on visual representation of equations

Wednesday

  • Worked on presentation
  • Literature research on sexual dimorphism information and verification
  • Visual representation of equations

Thursday

  • Attended other students' midpoint presentations
  • Updated wiki
  • Attended graduate student's Master's thesis presentation

Friday

  • OFF (Fourth of July holiday)

Week 6 / / 7.6-10

Monday

  • Research on nonlinear systems & equilibrium points
  • TikZ
  • Writing about equations

Tuesday

  • Writing about equations
  • RCR training
  • Evaluated L as a function of SAT

Wednesday

  • Writing about equations
  • MATLAB
  • Met with Dr. Merrill

Thursday

  • MATLAB simulations

Friday

  • Updated wiki
  • MATLAB simulation

Week 7 / / 7.13-17

Monday

  • Mathematical analysis of cases of SAT values and their relationships with inflammation and leptin

Tuesday

  • Analysis of cases
  • Writing for final paper
  • Read literature about possible applications of the model

Wednesday

  • Read literature about possible applications of the model
  • Met with Dr. Merrill
  • Writing about system of equations
  • Phase plane analyses of cases
  • MATLAB simulations of cases

Thursday

  • Writing about cases
  • MATLAB simulations of cases

Friday

  • Writing about cases
  • Writing: motivation, introduction, research goals

Week 8 / / 7.20-24

Monday

  • Writing final paper
  • Reading literature related to potential applications of the model
  • Making connections between model and its applications
  • MATLAB simulations

Tuesday

  • Meeting with Dr. Merrill
  • Writing final paper
  • Reading literature and making connections related to potential applications of the model
  • Compiling references

Wednesday

  • Writing proofs
  • Working on poster

Thursday

  • Writing paper
  • Working on poster

Friday

  • Meeting with Dr. Merrill
  • Working on poster

Week 9 / / 7.27-31

Monday

  • Poster
  • Paper

Tuesday

  • Paper

Wednesday

  • Writing paper and formatting it for journal submission

Thursday

  • Formatting for journal
  • Compiling references

Friday

  • Formatting for journal
  • Working on presentation