Engineering a tethering system in African trypanosome

Are you interested in the project below? Awesome! PLEASE DO NOT APPLY THROUGH THE URO SITE. Instead, send in your application using this google form by Feb 20. PIs will then contact you if you have been selected for an interview.

Project 2 Engineering a tethering system to probe gene regulatory mechanisms in the African trypanosome.

We are globally interested in how organisms adapt to different environments. Our study system is the African trypanosome parasite, which cycles between a tsetse fly vector and a mammalian host. In humans and animals, the parasite causes a fatal disease called African trypanosomiasis (sleeping sickness). In order to adapt itself from living in the bloodstream to living in the fly, the parasite must change the transcript levels of thousands of genes in the genome. We want to know more about the molecular mechanisms behind these changes.

In this project we are interested in understanding the effect of tethering a chromatin interacting protein to a particular gene locus. Chromatin is made up of DNA and proteins around which the DNA is wrapped. We have previously showed that chromatin interacting bromodomain proteins are essential to maintain immune evasion for parasites living in the mammalian bloodstream. We have performed experiments to show that when parasites transition from the bloodstream to the insect stage, bromodomain protein 3 (Bdf3) localizes to a region of the genome that houses the gene for an insect stage specific surface protein. We hypothesize that Bdf3 localization to this region might facilitate the transcription of this insect-stage specific gene. To test this, we want to use a CRISPR system to tether Bdf3 to this locus in bloodstream parasites, a stage in which the insect-specific proteins should be silenced. An increase in transcription of the gene following artificial tethering of Bdf3 would support the model that chromatin interacting proteins regulate transcript levels of life cycle stage-specific genes.

Be warned, this project is not for the faint of heart. While others have CRISPR systems up and running in trypanosomes, our lab has not yet performed this type of experiment. Tolerance for troubleshooting is therefore a must. Techniques that will be used in this project include sterile parasite culture (equivalent to tissue culture for mammalian cells), flow cytometry, genetic modification of the parasite genome, and engineering novel plasmids to set up the CRISPR system.

To complete your application for summer research in Biology, submit this google form  by Feb 20.

Name of research group, project, or lab
Schulz Lab
Why join this research group or lab?

Why work in the Schulz Lab?

We aim to understand how the parasites adapt to different environments in the fly and mammalian bloodstream, with an eye toward manipulating this adaption to help fight human disease. African trypanosomiasis affects the rural poor, and new drugs are urgently needed. However, drug companies are not highly motivated to produce drugs for people that can’t pay for them. We hope that by understanding more about parasite adaption, we can improve the lives of many living in regions of Sub-Saharan Africa where African trypanosomiasis is endemic.

The research in our lab is aimed toward publication in peer reviewed journals. In the last 5 years, 12 undergraduate students have been co-authors on our published papers. In addition to learning how to design and perform experiments, students in the Schulz lab practice the art of presenting science in a variety of formats, from posters, to talks, to publications. We strive for a rigorous and highly supportive experience.

Representative publication
Logistics Information:
Project categories
Biology
Student ranks applicable
Sophomore
Junior
Senior
Student qualifications

Completion of Bio52 and Bio23 required. Pipetting experience helpful. Some experiments run 4-5 hours without long breaks. 

Time commitment
Summer - Full Time
Compensation
Paid Research
Number of openings
2
Techniques learned

Techniques that will be used in this project include sterile parasite culture (equivalent to tissue culture for mammalian cells), flow cytometry, genetic modification of the parasite genome, and engineering novel plasmids to set up the CRISPR system.

Contact Information:
Mentor name
Danae Schulz
Mentor email
dschulz@hmc.edu
Mentor position
Principle Investigator
Name of project director or principal investigator
Danae Schulz
Email address of project director or principal investigator
dschulz@g.hmc.edu
2 sp. | 0 appl.
Hours per week
Summer - Full Time
Project categories
Biology