Transgenic approach to improved productivity:
Establishing African Trypanosomiasis resistance in cattle by a
transgenic ap...
The problem
African Trypanosomiasis
• Caused by extracellular protozoan
parasites – Trypanosoma
• Transmitted between mamm...
The problem
Vector Control (Tsetse Fly)
• Using toxic insecticide
• Negative impacts on environment
• Not sustainable
• Ex...
Establish African Trypanosomiasis Resistance in Cattle by A
Transgenic Approach
• Establish a transgenic cattle model with...
Innovation in the work
• Using a transgenic approach to create disease
resistance in cattle
• The method is once for all a...
Links to ILRI’s SO and CGIAR SLO
Tryps Resistant Cow
Delivery partners needed

ILRI SO:
Better lives
through livestock

Sm...
Importance to ILRI
•

Improved capacity with new technology
(cloning) platform

•

Being the lead in transgenic livestock ...
Project Process
Kenya
Boran

Genomic locus of
Baboon apoL-I gene
Vector construction

ILRI
Bovine embryonic fibroblasts
(B...
Results
Two Cloned Calves born through Caesarean Section
ID: Tatu
Date of Birth: 16 July 2012 (Kapiti)
Sex: Male
Birth Wei...
15-Month

At Birth

CL001 (Tumaini)
Fund & Partnership
This work is funded by

US National Science Foundation
&
BREAD Program

RDA-ILRI Fund
(Korean)

It is i...
Where to from now?
Current Project

Potential Future Projects

Transfection of Boran BEFs line
(Roslin Institute, UK)

Bio...
Potential opportunities
More application of established cloning platform
• Improve cattle genetics through traits introduc...
General discussion (facultative)
Resource mobilization strategy
• Trypanoresistant cow project – wait and see
• Traits int...
better lives through livestock
ilri.org

The presentation has a Creative Commons licence. You are free to re-use or distri...
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Transgenic approach to improved productivity: Establishing African Trypanosomiasis resistance in cattle by a transgenic approach

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Presented by Mingyan Yu, Charity Muteti, Moses Ogugo and Steve Kemp at the ILRI BioSciences Day, Nairobi, 27 November 2013


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  • There MUST be a CGIAR logo or a CRP logo. You can copy and paste the logo you need from the final slide of this presentation. Then you can delete that final slide To replace a photo above, copy and paste this link in your browser: http://www.flickr.com/photos/ilri/sets/72157632057087650/detail/ Find a photo you like and the right size, copy and paste it in the block above.
  • Trypanosomes live and multiplyextracellularly in blood and tissue fluidsDistribution corresponds to the distribution of Tsetse flies – tsetse beltAlso a threaten for human.
  • Antigenic variation is transcriptional switching from one VSG gene to another.There are no prophylactic drugsNew idea for a sustainable way to control the disease
  • TLF only exists in primates. Gain resistance during evolution. Baboon is remarkably resistant to both animal and human infective species.Cattle also has the family of apoL, but no apoL1. Previous research with transgenic mice proved that baboon apoL-1 expression in mice can protect the mice from the tryps infection. We hypothesize that expression of baboon apoL-1 in cattle can protect cattle in the same way.
  • Cloning is a technology widely used in the developed countries that allows livestock breeders to create identical twins of their best animals and ensure that the herds are maintained at the highest quality and most productive level.
  • 11 BEFs cell lines were isolated, 6 female and 5 male. If it works, we could have more genetic diversity using different cells lines to make transgenic cows.We prefer male BEFs, because it is more efficient to spread the transgene in the cattle.To test the technique and suitability of Boran for cloning, we tried cloning using original BEFs without transgene.
  • Once the cloned animal survives, they are normal and can breed naturally.
  • Transgenic approach to improved productivity: Establishing African Trypanosomiasis resistance in cattle by a transgenic approach

    1. 1. Transgenic approach to improved productivity: Establishing African Trypanosomiasis resistance in cattle by a transgenic approach Mingyan Yu, Charity Muteti, Moses Ogugo, Steve Kemp Animal Biosciences, ILRI ILRI BioSciences Day, Nairobi, 27 November 2013 Partner go New York University Roslin Institute/ University of Edinburgh Michigan State University
    2. 2. The problem African Trypanosomiasis • Caused by extracellular protozoan parasites – Trypanosoma • Transmitted between mammals by Tsetse flies (Glossina sp.) • Prevalent in 36 countries of subSahara Africa. http://www.imib-wuerzburg.de/research/siegel/research/ Trypanosomes in Blood stream In cattle • A chronic debilitating and fatal disease. • A major constraint on livestock and agricultural production in Africa. • Costs US$ 1 billion annually. In human (Human Sleeping Sickness) • Fatal • 60,000 people die every year • Both wild and domestic animals are the major reservoir of the parasites for human infection. http://www.bio.davidson.edu/courses/immunology/students/spring2006/ryan/termpaper.html
    3. 3. The problem Vector Control (Tsetse Fly) • Using toxic insecticide • Negative impacts on environment • Not sustainable • Expensive Vaccine • Tryps periodically change the major surface antigen – variant surface glycoprotein (VSG) and evade the host immune system. • More than 2 decades, there is no effective vaccine developed. Drug • No prophylactic drugs • Drug toxicity and resistance • Expensive New idea
    4. 4. Establish African Trypanosomiasis Resistance in Cattle by A Transgenic Approach • Establish a transgenic cattle model with African Trypanosomiasis resistance using nuclear transfer (cloning). • On the background of a Kenyan indigenous breed – Kenyan Boran. • Introduce the gene – apoL-I from Baboon into Boran, which is the key trypanolytic component of Baboon’s protective Trypanosome Lytic Factor (TLF) against both cattle and humaninfective trypanosomes.
    5. 5. Innovation in the work • Using a transgenic approach to create disease resistance in cattle • The method is once for all and self-sustainable - Once the resistance is established, it could be transmitted to the next generations through normal breeding.
    6. 6. Links to ILRI’s SO and CGIAR SLO Tryps Resistant Cow Delivery partners needed ILRI SO: Better lives through livestock Small-scale Farmers Improved livestock productivity More meat and milk More income from sales SLO3 Improve nutrition and health Improved crop productivity SLO2 Improve food security CRP 3.7 – Genetic component SLO1 Reduce rural poverty CGIAR System Level Outcomes 6
    7. 7. Importance to ILRI • Improved capacity with new technology (cloning) platform • Being the lead in transgenic livestock research in Africa (challenge & opportunity) • Improved public visibility and image by resolving the persistent trypanosomiasis problem 7
    8. 8. Project Process Kenya Boran Genomic locus of Baboon apoL-I gene Vector construction ILRI Bovine embryonic fibroblasts (BEF) primary culture Roslin Institute Validate the construct in transgenic mouse Transfection & screening apoL-I Transgenic BEFs (male) Nuclear Transfer ILRI (cloning) Transgenic calves Phenotyping Trypanosome resistant transgenic Boran bull New York University Michigan State University
    9. 9. Results Two Cloned Calves born through Caesarean Section ID: Tatu Date of Birth: 16 July 2012 (Kapiti) Sex: Male Birth Weight: 46 kg Date of Death: 19 July 2012 (74 hrs) Cause of death: Low temperature, low blood glucose … ID: CL001 (Tumaini) Date of Birth: 21 August 2012 (ILRI) Sex: Male Birth Weight: 35 kg Current age: 15 months, healthy
    10. 10. 15-Month At Birth CL001 (Tumaini)
    11. 11. Fund & Partnership This work is funded by US National Science Foundation & BREAD Program RDA-ILRI Fund (Korean) It is implemented in a partnership with New York University Michigan State University Roslin Institute, University of Edinburgh
    12. 12. Where to from now? Current Project Potential Future Projects Transfection of Boran BEFs line (Roslin Institute, UK) Biosafety Research • Confirm no health risk of the gene to the transgenic cow • Confirm the safety of meat and milk consumption of the apoL1 transgenic cow Establish Apol-I Transgenic Boran by nuclear Transfer with Transgenic Cells Phenotyping (confirm Tryps resistance) • ApoL-I expression pattern • Killing of Trypanosomes in vitro (serum) and in vivo (challenge) • Monitor the health conditions with growth Increase Genetic Diversity • Establish more transgenic cattle with Kenya Boran BEFs lines • Establish transgenic cattle with other Kenyan indigenous breeds Transgene Delivery • Develop a breeding programme to disseminate the transgene to farmers
    13. 13. Potential opportunities More application of established cloning platform • Improve cattle genetics through traits introduction between breeds - Using TALENs and cloning together to introduce good traits between breeds to obtain efficient cross-breeding. • Indigenous breeds conservation - Establish a bank of cells from indigenous breeds of cattle, sheep and goats, which are capable of cloning. • Training for other African regions - Make good use of the technique to maintain the best animal genetics and improve the livestock productivity in Africa.
    14. 14. General discussion (facultative) Resource mobilization strategy • Trypanoresistant cow project – wait and see • Traits introduction between breeds using TALENs seeking collaboration and new traits What support do you expect from ILRI and the BioScience Directorate? • Effective communications with the public regarding the transgenic cow project in due course.
    15. 15. better lives through livestock ilri.org The presentation has a Creative Commons licence. You are free to re-use or distribute this work, provided credit is given to ILRI.

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