The professor of medicine, who has been in charge at the trust since 2003, will take over from Sir John Beddington in April 2013.
Before joining the trust, Sir Mark was head of the division of medicine at Imperial College London.
The immunologist is already familiar with the workings of government: he sits on the Prime Minister’s Council for Science and Technology and has led independent reviews on the use and sharing of personal information, and on science and maths education in secondary schools.
He is also a member of advisory boards including the India-UK CEO Forum and is a non-executive member of the Office for Strategic Coordination of Health Research.
During his time at the Wellcome Trust, where he has been in charge of an annual budget of around ?600 million, Sir Mark has been a strong champion of open access and public engagement.
Under his stewardship, the trust changed policy to commit its grantees to publishing their work in open-access journals, and in 2007 it opened the Wellcome Collection, a London venue for exhibitions of work connecting medicine, life and art.
At the Wellcome Trust, Sir Mark also showed himself adept at dealing with the media, acting as a spokesman on issues ranging from animal research to fertility treatments.
“I look forward to working with colleagues both inside and outside government to ensure that the best possible advice can be provided from the most expert sources, based on the strongest evidence, to facilitate the wisest possible policy decisions,” said Sir Mark, commenting on the announcement.
Writing on the social networking site Twitter, his predecessor Sir John said he was delighted at the appointment. “He’s a long time colleague and friend. I look forward to working with him,” he wrote.
The decision was generally welcomed by science policy chiefs. Sir Paul Nurse, president of the Royal Society, added that in Sir Mark “we have absolutely the right person for the job”.
The Wellcome Trust said that Sir William Castell, chairman of the trust’s board of governors, would lead efforts to find a new director to succeed Sir Mark.
Meanwhile, the Wellcome Trust has also confirmed measures to toughen up its open access policy.
As first reported in Times Higher Education in March, the trust will withhold final grant payments if institutions do not guarantee that all papers produced with Wellcome funding will be made open access. It will also refuse further funding to any researcher with non-compliant papers.
The changes, effective immediately, are a response to the relatively low compliance rate – 55 per cent – with the open access policy the trust adopted in 2006.
The policy requires that all papers funded even in part by the trust are made available via the UK PubMed Central repository within six months of publication.
From 2013, the trust will also require publishers to make papers available for all kinds of reuse, including for commercial activity.