Scientific Research Project Title

Intelligent and Artificial Designer Cells & Organs for Regenerative Transplant Medicine (iART)

Research Institution

Aarhus University

Department of Biomedicine

RESEARCH FIELD

Xenotransplantation, Genome Editing, Animal Biotechnology, Regenerative Medicine

CONTACT INFO

Phone: +45 87167015
E-mail: lin.lin@biomed.au.dk

Research leader

Lin Lin

Ph.D, Assistant Professor, born 1984

Project title

Technologies for pig-to-human organ transplantation. 

What is your project about?

One greatly unmet need in transplant medicine is the shortage of organs. Pigs have been regarded as one of the most promising alternative organ sources due to their anatomical and physiological similarities with humans. However, risks of viral transmissions and human immune rejections of pig xenografts are the two major barriers for pig-to-human organ transplantation, also known as xenotransplantation. Following my previous success of inactivating all porcine endogenous retro viruses (PERV) in pigs using CRISPR gene editing and cloning, my current project will develop technologies to generate pigs that will be resistant to human immune rejections and viral infections through gene editing and genome recoding approaches.

How did you become interested in your particular field of research?

Two decades ago, I was fascinated by “Dolly the sheep” which made me decided to conduct a PhD study on pig cloning technologies and generating genetically modified pigs for biomedicine. I was particularly interested in using pigs as an alternative organ donor. Six years ago, breakthroughs in gene editing technology, CRISPR-Cas9, made me decided to work on xenotransplantation and subsequently collaborate with Professor George Church on this particular field. With all the technologies I have acquired, I feel that it’s my responsibility to make pigs becoming the solution for organ transplantation.

What are the scientific challenges and perspectives in your project?

One remaining challenge in pig-to-human organ transplantation is the human immune rejection of xenografts. Currently, over 20 genetic modifications have been identified as xenoprotective. However, it’s still unknown which combination of these genetic modifications will give the best xenoprotective effect. Besides, tissue-specific immune rejection and xenograft survival suggest that there are still unknown xenoprotective genes. My project combines single endothelial cell RNA sequencing and genome-wide CRISPR genetic screening to identify xenoprotective genes. The established cell and CRISPR screening platforms will identify the best combination of xenoprotective modifications. Furthermore, my project will apply genome recoding to generate xenoprotective and viral resistant pigs for transplantation. 

What is your estimate of the impact, which your project may have to society in the long term?

First, from the fundamental science point of view, my project will lead to a better understanding of human immune rejection of xenografts. Second, technologies developed in my project will facilitate the generation of genetically modified pigs that can be used in organ transplantation. Third, my project will lead to generation of the best genetically modified pigs for xenotransplantation. This will provide solutions to the increasing crisis of organ shortage in our society. In my project, I will establish several technologies to achieve breakthroughs towards xenotransplantation, of which some of the technologies and outcomes are expected to be transferred to companies. 

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

As a young scientist, I am so grateful for the support of the Sapere Aude programme. This will undoubtedly have a great impact on my future academic career. The Sapere Aude programme firstly encourages me to further develop my particular field of research and supports me establishing my own research group. With the support from the Sapere Aude programme, I will be able to achieve more breakthroughs in xenotransplantation, to recruit more project supports from ERC, and to become a top scientist within my field of research in the future.    

Background and personal life

I am from China and have been living in Denmark for more than 10 years. Being the mother of two children, Mikkel (4.5-year old, Chinese name Mingke (明可) and Viktor (almost 2-year old, Chinese name Mingxuan (明轩)), I now spend most of my spare time playing with the kids. 

City of current residence
Aarhus, Denmark

High school
Institute of Human Genetics, Aarhus University, PhD
Beijing Institute of Genomics, Chinese Academy of Science, MSc
China Agricultural University, BSc 
ShiShi High School, Chengdu, China