BREAD: Basic mechanisms underlying species‐specific trypanosome resistance

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Unlocking livestock development potential through science, influence and capacity development ILRI APM, Addis Ababa, 15-17 May 2013 Developing capacity Influencing decisions BREAD: Basic Mechanisms Underlying Species‐Specific Trypanosome Resistance This document is licensed for use under a CreaAve Commons ACribuAon‐Noncommercial‐Share Alike 3.0 Unported Lisence May 2013 Strategic lessons on Build the capacity of Africa in the technique of nuclear transfer which is a powerful tool for superior gene7c traits preserva7on and improvement. Provide policy makers with adequate informa7on in regard of gene7cally modified ca>le. Mingyan Yu, Charity Mute0, Moses Ogugo, Stephen Kemp Gene$cs Group, Biosciences, Interna$onal Livestock Research Ins$tute Delivering science: Good communica7on to win public understanding and government authority support is important. Synergy with exis7ng technical capacity of other groups is an important factor to the project success. Main message We propose a new strategy for crea7ng resistance in ca>le to African trypanosomiasis, a major disease that affects agricultural produc7on in broad regions of Africa. The long‐term aim is to generate gene7cally modified ca>le, which carry a gene that imparts resistance to African trypanosomes. The gene, APOL1, encodes the key trypanoly7c component of Baboon’s protec7ve Trypanosome Ly7c Factor (TLF) against both ca>le and human‐infec7ve trypanosomes. TLFs are only found in humans, gorillas, sooty mangabys, mandrills and baboons and govern resistance to different African trypanosome species. Baboons are remarkably resistant to all African trypanosomes due to baboon TLF, specifically baboon apoL‐I. Approach Using the technique of soma7c cell nuclear transfer (cloning), to establish a transgenic ca>le model with resistance to African Trypanosomiasis on the background of the Kenyan indigenous breed – Kenyan Boran. Achievement Eleven (6 female & 5 male) bovine embryonic fibroblasts (BEFs) were established and shipped to the partner for gene modifica7on. Nuclear transfer (cloning) plaYorm was established and tested. Two cloned calves (male) were born. One cloned calf survives up to date (8‐month old) and is in good condi7on. Partners Jayne Raper Hunter College, City University of New York Alan Archibald Roslin Ins7tute, University of Edinburgh Jose Cibelli Michigan State University Expected impacts on farmers Trypanosome resistant caCle will survive in the tsetse belt of Africa (10 million square miles) and reduce the transmission of human infec7ve trypanosomes causing human sleeping sickness. Increased crop producAon: the farmers, especially the women who 7ll the land by hand (90% of sub‐Saharan Africa) can use ca>le for haulage, trac7on and soil fer7lity. More food and nutriAon: less vulnerable to cri7cal harvest 7me imposed by plants. More income: have a store of wealth for future investments BEFs (DNA donor) Oocyte (Egg recipient) Remove nucleus (Enuclea7on) Transfer the cell Reconstructed Embryo Embryo Transfer 278 Days Cloned Calves born ID Tatu ID Tumaini (CL001) apoL‐I Tryps lysed Tryps Survived 3 days 8‐month

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Poster prepared by Mingyan Yu, Charity Muteti, Moses Ogugo and Stephen Kemp for the ILRI APM 2013, Addis Ababa, 15-17 May 2013

Transcript of BREAD: Basic mechanisms underlying species‐specific trypanosome resistance

Page 1: BREAD: Basic mechanisms underlying species‐specific trypanosome resistance

Unlocking livestock development potential through science, influence and capacity development ILRI APM, Addis Ababa, 15-17 May 2013

Developing capacity Influencing decisions

BREAD: Basic Mechanisms Underlying Species‐Specific Trypanosome Resistance 

This document is licensed for use under a CreaAve Commons ACribuAon‐Noncommercial‐Share Alike 3.0 Unported Lisence        May 2013 

Strategic lessons on 

Build the capacity of Africa in the technique of nuclear transfer which is a powerful tool for superior gene7c traits preserva7on and improvement. 

Provide policy makers with adequate informa7on in regard of gene7cally modified ca>le. 

Mingyan Yu, Charity Mute0, Moses Ogugo, Stephen Kemp 

Gene$cs Group, Biosciences, Interna$onal Livestock Research Ins$tute 

Delivering science:

  Good communica7on to win public understanding and government authority support is important. 

  Synergy with exis7ng technical capacity of other groups is an important factor to the project success. 

Main message We propose a new strategy for crea7ng resistance in ca>le to African  trypanosomiasis,  a  major  disease  that  affects agricultural produc7on in broad regions of Africa.  

The  long‐term aim  is  to  generate  gene7cally modified  ca>le, which  carry  a  gene  that  imparts  resistance  to  African trypanosomes. The gene, APOL1, encodes the key trypanoly7c component  of  Baboon’s  protec7ve  Trypanosome  Ly7c  Factor (TLF)  against  both  ca>le  and  human‐infec7ve  trypanosomes. TLFs  are  only  found  in  humans,  gorillas,  sooty  mangabys, mandrills  and  baboons  and  govern  resistance  to  different African  trypanosome  species.  Baboons  are  remarkably resistant  to  all  African  trypanosomes  due  to  baboon  TLF, specifically baboon apoL‐I. 

Approach Using the technique of soma7c cell nuclear transfer (cloning), to  establish  a  transgenic  ca>le  model  with  resistance  to African  Trypanosomiasis  on  the  background  of  the  Kenyan indigenous breed – Kenyan Boran. 

Achievement   Eleven  (6  female  &  5  male)  bovine  embryonic  fibroblasts 

(BEFs) were established and shipped to the partner for gene modifica7on. 

  Nuclear  transfer  (cloning)  plaYorm  was  established  and tested. 

  Two cloned calves (male) were born.   One cloned calf survives up to date (8‐month old) and is in 

good condi7on.  

Partners Jayne Raper   Hunter College, City University of New York Alan Archibald   Roslin Ins7tute, University of Edinburgh Jose Cibelli   Michigan State University 

Expected impacts on farmers 

  Trypanosome resistant caCle will survive in the tsetse belt of  Africa  (10  million  square  miles)  and  reduce  the transmission  of  human  infec7ve  trypanosomes  causing human sleeping sickness. 

  Increased  crop  producAon:  the  farmers,  especially  the women  who  7ll  the  land  by  hand  (90%  of  sub‐Saharan Africa) can use ca>le for haulage, trac7on and soil fer7lity. 

 More food and nutriAon: less vulnerable to cri7cal harvest 7me imposed by plants. 

 More  income:  have  a  store  of  wealth  for  future investments 

BEFs (DNA donor) 

Oocyte (Egg recipient) 

          Remove nucleus        (Enuclea7on) Transfer the cell 

Reconstructed Embryo 

Embryo Transfer 278 Days 

Cloned Calves born 

ID Tatu  ID Tumaini (CL001) 

apoL‐I 

Tryps lysed 

Tryps 

Survived 3 days 

8‐mon

th