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==Research Overview==
==Research Overview==
The Zhang lab at the UCSD Bioengineering department is interested in developing novel genome technologies towards the applications in personalized genome medicine and stem cell research.  
The Zhang lab at the UCSD Bioengineering department is interested in developing novel genome technologies towards the applications in stem cell research, brain mapping and human disease studies.


===Genome Technology:===  
===Genome Technology:===  
We are developing various methods for synthesis, manipulation and sequencing of DNA molecules. Examples include  
We are developing various methods for synthesis, manipulation and sequencing of DNA molecules. Examples include  
* large-scale DNA synthesis on programmable DNA chips;  
*single-cell genome sequencing;
* isolation, amplification and sequencing of single chromosomal molecules;
*single-cell transcriptome sequencing;
* digital profiling of gene expression and allele-specific gene expression;  
*large-scale DNA synthesis on programmable DNA chips;
* targeted genome capture and sequencing.
*targeted digital analysis of epigenome;
* targeted digital analysis of epigenome.
*imaging and cell tracking.
===Genome Informatics:===  
===Genome Informatics:===  
Almost every single aspect of our genome-scale studies depends on bioinformatics.  We do large-scale "manipulation" of DNA molecules in computer <b>before and after</b> processing them in test tubes. Here are some examples:
Almost every single aspect of our genome-scale studies depends on bioinformatics.  We do large-scale "manipulation" of DNA molecules in computer <b>before and after</b> processing them in test tubes. Here are some examples:
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* mapping and analysis of next-generation DNA sequencing data;
* mapping and analysis of next-generation DNA sequencing data;
* de novo assembling of single-cell genome sequencing data;
* de novo assembling of single-cell genome sequencing data;
* haplotype assembling and analysis of single molecule sequencing data.  
* haplotype assembling and analysis of single molecule sequencing data;
* image analysis (segmentation, feature identification and registration, quantitative analysis);
* integrative analysis of transcriptomics, epigenomics and genomics data.
 
===Biology:===
===Biology:===
====Personalized regenerative medicine====
====Single-cell analysis of human brain.====
Our research interest lies in the genetics of individuality. We ask what are the phenotypic differences among human individuals or cell lines derived from these individuals, and what are the genetic factors that can explain such differences (formally termed as phenotypic variations). We seek to identify functional genetic variations in the human genome, which often contribute to the susceptibility of human complex diseases. We use a system biology approach by combining large-scale genotyping, phenotyping, functional assays, and analysis of gene regulation networks or pathways.
Human brain is arguably the most complex organ of the body. We are applying single-cell sequencing and imaging techniques to characterize the transcriptional diversity and somatic genomic variation of the human brain, and to related such -omics information to the three dimensional organization of the human cortex.  
 
====Regenerative medicine====
We perform these studies under two different contexts:
Recent advances in nuclear programming and reprogramming have provided extremely powerful tools for manipulating the cell fates. A holy grail of regenerative medicine is to restore damaged tissues or organs with another cell type from the same patients with the use of nuclear reprogramming and genetic engineering techniques. We are particularly interested in characterizing the process of cell fate conversion, understanding the underlying molecular mechanisms.
* Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPS):
====Genetic and environmental determinants for human common diseases.====
**We are performing large-scale phenotyping and functional genomic analyses on a panel of hESC lines established at the Harvard Stem Cell Institute (HUES lines).  
Another very broad area of our research interest is to understand genetic and environmental factors that contribute to common human diseases. For genetic factors, we are focusing on cis-regulatory genetic variants in the human genome. On the environmental aspect, we are particularly interested in the microorganisms that reside in different parts of the human body, also called human microbiome. We are also working on the characterization of the epigenome, which is an important layer of cellular memory that captures the effects of both genetic and environmental factors.
**We are also performing genomic analyses of iPS cells to understand the de-differentiation and re-differentiation processes. Our thrust along this line has recently been recognized and supported by the [http://nihroadmap.nih.gov/epigenomics/  NIH Epigenomics RoadMap program].
* [http://www.personalgenome.org Personal Genome Project]: we have received UCSD's IRB approval to perform functional analyses on the samples collected under the Personal Genome Project. Another web site about [http://thepersonalgenome.com PGP], which has a link to a [http://video.google.com/googleplayer.swf?docId=7705521558720943852:903000:2276000&#038;hl=en video clip of Esther Dyson on the Charlie Rose Show] talking about PGP.
 
====Human microbiome====
It has been recognized in the past few years that the distribution and activities of microorganisms in the human body (human microbiome) have profound impacts on the health of the host. Because of the important implications of this research area in public health, NIH recently launched a cross-institutional [http://nihroadmap.nih.gov/hmp/ Human Microbiome Project] under its RoadMap Initiatives.
 
Analyzing the complex communities of these microorganisms has been very challenging, partly because most microorganisms are difficult to grow and maintain in laboratory culturing conditions. Supported by the Human Microbiome Project, we are developing an efficient and scalable method to obtain genome information from single cells in such complex microbial communities. This is a collaborative project with [http://fleece.ucsd.edu/~ylo/ Dr. Yuhwa Lo]'s laboratory in the UCSD ECE department. It involved seamless integration of methods in several areas including microbiology, genomics, biophotonic, signal processing and nanofabrication.


===Potential graduate student rotation projects:===  
===Potential graduate student rotation projects:===  
* Design and fabrication of microfluidic devices for single chromosome analysis.  
*Design and fabrication of microfluidic devices for single cell analysis.
* Development of remapping strategies for next-generation DNA sequencing data.
*Computational analysis of single-cell transcriptome data sets.
* Analysis of global epigenetic changes in stem cells.
*Epigenetic analysis of human brain and stem cells.
*Live cell imaging and image analysis.

Latest revision as of 22:10, 27 February 2014

Research Overview

The Zhang lab at the UCSD Bioengineering department is interested in developing novel genome technologies towards the applications in stem cell research, brain mapping and human disease studies.

Genome Technology:

We are developing various methods for synthesis, manipulation and sequencing of DNA molecules. Examples include

  • single-cell genome sequencing;
  • single-cell transcriptome sequencing;
  • large-scale DNA synthesis on programmable DNA chips;
  • targeted digital analysis of epigenome;
  • imaging and cell tracking.

Genome Informatics:

Almost every single aspect of our genome-scale studies depends on bioinformatics. We do large-scale "manipulation" of DNA molecules in computer before and after processing them in test tubes. Here are some examples:

  • designing DNA probes for capturing & sequencing SNPs/Exons, which also includes various simulation;
  • mapping and analysis of next-generation DNA sequencing data;
  • de novo assembling of single-cell genome sequencing data;
  • haplotype assembling and analysis of single molecule sequencing data;
  • image analysis (segmentation, feature identification and registration, quantitative analysis);
  • integrative analysis of transcriptomics, epigenomics and genomics data.

Biology:

Single-cell analysis of human brain.

Human brain is arguably the most complex organ of the body. We are applying single-cell sequencing and imaging techniques to characterize the transcriptional diversity and somatic genomic variation of the human brain, and to related such -omics information to the three dimensional organization of the human cortex.

Regenerative medicine

Recent advances in nuclear programming and reprogramming have provided extremely powerful tools for manipulating the cell fates. A holy grail of regenerative medicine is to restore damaged tissues or organs with another cell type from the same patients with the use of nuclear reprogramming and genetic engineering techniques. We are particularly interested in characterizing the process of cell fate conversion, understanding the underlying molecular mechanisms.

Genetic and environmental determinants for human common diseases.

Another very broad area of our research interest is to understand genetic and environmental factors that contribute to common human diseases. For genetic factors, we are focusing on cis-regulatory genetic variants in the human genome. On the environmental aspect, we are particularly interested in the microorganisms that reside in different parts of the human body, also called human microbiome. We are also working on the characterization of the epigenome, which is an important layer of cellular memory that captures the effects of both genetic and environmental factors.

Potential graduate student rotation projects:

  • Design and fabrication of microfluidic devices for single cell analysis.
  • Computational analysis of single-cell transcriptome data sets.
  • Epigenetic analysis of human brain and stem cells.
  • Live cell imaging and image analysis.
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