Cheng, Ryan R

Cheng Lab Introduction

My research group leverages techniques from statistical mechanics, biopolymer theory, and machine learning to unravel the mechanistic principles of genome organization and transcriptional regulation. I am particularly interested in the organization of genetic material within the nuclei of eukaryotic cells and how various biomolecular interactions shape that organization and function, thereby affecting how that genetic material is read and maintained. This type of understanding is still in its infancy but has far-reaching applications. For example, the disruption of specific biomolecular interactions has already been implicated in several known human maladies. Further, all known life forms use DNA to store genetic information, and all living things have universal aspects of regulation, storage, and function. Over the next several years, my research group will focus on three biophysical problems central to a quantitative understanding of the biomolecular interactions that shape the human genome and its function—e.g., how our genome works.

My research group will build an “interactome” of the biomolecules in the nucleus. These biomolecules play essential roles in regulating/maintaining the genome. Using biomolecular data, particularly sequencing data, we will identify the signals for biomolecular interactions that have been maintained over the course of natural selection. Furthermore, we will use a combination of machine learning and molecular simulations to create structural models of these biomolecular interactions, particularly in cases where no known structure exists.

Taking advantage of the recent boom in genome imaging, we will construct three-dimensional polymeric models of the genome that are constrained to be consistent with experimental snapshots to quantify, interpret, and build physical theories of the chromosomal structure-to-function relationship.

Using a state-of-the-art computational model of the genome, my research group will explore how external forces applied to the nuclear membrane modulate chromosomal structures and dynamical motions. Disruption of the physical links that connect chromatin to the cytoskeleton has been shown to lead to various diseases, including laminopathies. However, what remains unclear is the mechanistic role of these links and how forces transduced across them play important roles in the normal function of the nucleus.

Projects:

The cellular interactome: building structural models of biomolecular interactions that play important roles in maintaining, regulating, and organizing the genome

My research group will build an “interactome” of the biomolecules in the nucleus. These biomolecules play essential roles in regulating/maintaining the genome. Using biomolecular data, particularly sequencing data, we will identify the signals for biomolecular interactions that have been maintained over the course of natural selection. Furthermore, we will use a combination of machine learning and molecular simulations to create structural models of these biomolecular interactions, particularly in cases where no known structure exists.

Personnel:

Ryan R Cheng

Students:

Devilal Dahal, PostDoc, Added on MCC cluster on 09/08/2023 

Yapa Sasindu Gunasinghe, Graduate, Added on MCC cluster on 09/08/2023 

Toward a structure-to-function relationship of the genome: modeling of experimental chromatin imaging data and transcriptional data

Taking advantage of the recent boom in genome imaging, we will construct three-dimensional polymeric models of the genome that are constrained to be consistent with experimental snapshots to quantify, interpret, and build physical theories of the chromosomal structure-to-function relationship. 

Personnel:

Ryan R Cheng

Students:

Devilal Dahal, PostDoc, Added on MCC cluster on 09/08/2023 

Yapa Sasindu Gunasinghe, Graduate, Added on MCC cluster on 09/08/2023 

The Nucleus as a Mechano-sensor: modulation of chromosome structures via mechano-sensing

Using a state-of-the-art computational model of the genome, my research group will explore how external forces applied to the nuclear membrane modulate chromosomal structures and dynamical motions. Disruption of the physical links that connect chromatin to the cytoskeleton has been shown to lead to various diseases, including laminopathies. However, what remains unclear is the mechanistic role of these links and how forces transduced across them play important roles in the normal function of the nucleus.

Personnel:

Ryan R Cheng

Students:

Devilal Dahal, PostDoc, Added on MCC cluster on 09/08/2023 

Yapa Sasindu Gunasinghe, Graduate, Added on MCC cluster on 09/08/2023 

Computational Methods:

My group primarily focuses on coarse-grained simulations of genomic material, where chromosomes are described as block copolymers using the Minimal Chromatin Model (MiChroM). This previously developed model will serve as the starting point for our theoretical descriptions of chromosomal organization.

Software:

Simulations conducted using GROMACS and OpenMM.  Large-scale simulations will be run using OpenMM.

Collaborators:

Matheus Mello, a physics PhD student at Rice University working with Jose N. Onuchic. 

We are currently investigating the spatial positioning of chromosomes in a collection of imaged cells.

Ben Ruben, a physics PhD student at Harvard.

Our collaboration originated while we were both working at Rice University and focuses on the mechanical properties of chromosomes.

Michele Di Pierro, a professor at Northeastern. 

We are currently modeling chromatin immunoprecipitation experiments that probe which biomolecules bind to chromatin.

Mayu Shibata, a biology PhD student at Ochanomizu University.

We are working on building structural models using coevolutionary data, focusing primarily on bacterial signaling proteins.