Sander credits his move from theoretical physics to computational biology to Fred Sangers 1977 landmark paper in Nature', in which the nucleotide sequence of bacteriophage φX174 was published. Sander has made many contributions to the field of structural bioinformatics including developing tools such as the Families of Structurally Similar Proteins (FSSP) database and the DSSP algorithm for assigning secondary structure to the amino acids of a protein, given the atomic-resolution coordinates of that protein.
Sander was a founder of the biocomputing program at the European Molecular Biology Laboratory in Heidelberg, before moving the program to the European Bioinformatics Institute in Cambridge. He has served as chief information officer for the biopharmaceutical company Millennium Pharmaceuticals and has been an advisor to IBM's Deep Computing Initiative, which produced the Deep Blue chess computer.