DIMACS
DIMACS REU 2012

General Information

me
Student: Ethan Schwartz
Office: CoRE 442; Wright Rieman Labs A209B
School: Emory University
E-mail: eschwa9@emory.edu
Project: Chromatin Folding

Project Description

Within the nucleus of each cell lies DNA - an unfathomably long, twisted, and intricately coiled molecule - segments of which make up the genes that provide the instructions that a cell needs to operate. Crucial questions, however, remain regarding how the physical arrangement of the DNA in cells affects how genes work. In order to gain insight into the roles played by variuos proteins in reading and compacting the genome, we have developed new methodologies to simulate the dynamic, three-dimensional structures of long, fluctuating, protein-decorated strands of DNA. Our a priori approach to the problem allows us to determine the effects of individual proteins and their chemical modifications on overall DNA structure and function. The simulations account for the enhancement in communication detected experimentally on chromatin compared to protein-free DNA of the same chain length as well as the critical roles played by the cationic 'tails' of the histone proteins in this signaling. The states of chromatin captured in the simulations offer new insights into the ways that the DNA, histones, and regulatory proteins contribute to long-range communication along the genome.


Weekly Log

Week 1:
This week I met with Dr. Olson and the laboratory members to familiarize myself with the project and properly prepare for my presentation of the research.
Week 2:
This week I learned how to use Wolfram Mathematica, and was introduced to the simulation data. I then began calculating deformations (i.e. bending angle, twist) along the chromatin fiber at a base-pair resolution. This week we also took a trip to the IBM Corporation, in White Plains, NY. It was very interesting to see how modern, advanced computing technology, such as IBM's Watson, can also serve as a valuable medical tool, i.e. cross-referencing patient symptoms with databases of diseases and conditions.
Week 3:
This week I continued calculating the deformations (i.e. bending angle, twist) along the different chromatin fibers at a base-pair resolution. I also began calculating the atomic coordinates for each atom in the chromatin fiber, in order to visualize the fiber geometry.
Week 4:
This week I finished calculating the atomic coordinates for each chromatin fiber, in order to view a computer-generated model of the geometry of the chromatin fibers. I then calculated the deformations along the linker DNA in each chromatin fiber, in order to achieve insight into the average linker DNA in each simulation. I subsequently calculated the energy associated with the "middle" set of linker DNA in each chromatin fiber.
Week 5:
This week I continued calculating the energy associated with the "middle" set of linker DNA for each simulated chromatin fiber. I was also given additional configurational data from the simulations, and applied similar techniques as in prior weeks in order to gather the deformations and energy of the linker DNA. The final data for each simulation parameter was averaged, in order to achieve more convergent output data. This week we also took a field trip to the Cancer Institute of New Jersey (CINJ). It was very interesting to see the more analytical and computational side of cancer research, as well as the applied mathematics involved in cancer treatment, i.e. radiation oncology. In addition to the lectures on cancer research and treatment, we were given a tour of one of the laboraties, which contained a breeding center for genotypically varied zebrafish, as well as the treatment center.
Week 6:
This week I began a new analysis on the data sets: scoring the electrostatic interactions between the nucleosomes in each simulated chromatin fiber. The process involved parsing the protein frames for the nucleosomes from the configurational data; building, for each configuration, a global charge set for each nucleosome; and then scoring the electrostatic interactions between every nucleosomal charge for each nucleosome pair in each of the simulated chromatin fibers, using the Debye-Hückel potential equation (seen below). I started this process on the simulated fibers that did not have histone tails on the nucleosomes.
Eel({Qi}, {Qj}) = ΣkΣpφ(Qi[k], Qj[p]);
φ(q1, q2, Γ1, Γ2) = (k*q1*q2)*[(e-|Γ1 - Γ2|/λD) / (e0*|Γ1 - Γ2|)];
q1 = charge #1 valence, q2 = charge #2 valence, Γ1 = charge #1 location, Γ2 = charge #2 location;
k = 560.741, λD = 8.33, e0 = 80.00
Week 7:
This week I calculated the distances between nucleosome pairs, to complement the data for the internucleosomal interactions. I also finalized my data and prepared my final presentation.

Presentations


Additional Information