Fate decisions in stem cells

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About Fate decisions in stem cells

Description

Description

In spite of many technological advances current biological and genetic techniques are unable to directly link cell fate with the molecular state of individual cells. This project aims to determine the differences between individual stem cells by combining time-lapse microscopy, microfluidic cell culture, and single-cell RNA-seq. As a test case hematopoietic stem cells will be used, where there is evidence that fate decisions are determined by mechanisms that are self-propagating through many self-renewal divisions. Understanding the molecular basis of these mechanisms is fundamental to expand hematopoietic stem cells ex vivo, to develop safer and more effective gene therapy protocols, and to elucidate mechanisms of leukemogenesis in individual patients

The project

Single-cell RNA-seq offers a unique insight into the transcriptional state of individual cells that enables us to search for the molecular states that determine fate choices in stem cells and cancer cells. To gain real insight in these processes it is however not sufficient to measure the state of a cell, e.g. measure if a cell is in state A or B, but one must observe the process by which cells go from state A to B. To do so we have built a microfluidic platform that allows us to culture cells under time-lapse video microscopy and subsequently take these cell to perform single-cell RNA-seq while keeping track of their identities. We would like to characterize fate decisions in hematopoietic stem cells by analyzing differential gene expression patterns obtained from RNA-seq. We perform library preparation, where we introduce unique molecular identifiers to count molecules, and custom sequencing in our own lab. Analysis therefore from starts from raw reads and includes sorting them by index, counting molecules, alignment and finally preforming differential gene expression. In order to do so a fully functional pipeline should be developed which prepares the raw data for use with already existing alignment tools (bowtie etc.). As all experimental data and sequencing libraries are generated in the lab a student working on this project has the opportunity do some experimental work and prepare their own library and sequence it.

Requirements

  • Creativity and enthusiasm
  • Prior knowledge of sequence analysis
  • Affinity with molecular biology
  • Preferred start date around January 2015

Location

The lab is headed by Dr. Carl Hansen and consist of about 20 people. We’re at the Centre for high-throughput biology at the University of British Columbia in beautiful Vancouver, Canada. We closely collaborate with the BC cancer agency and have regular meetings so a student will also benefit from working together with these experts in the field of stem cell and cancer biology.

Contact details:

Want to know more send me an email:

Marijn van Loenhout

m.t.j.vanloenhout@gmail.com

www.chibi.ubc.ca/faculty/carl-hansen/hansen-lab/