Science | Thomas Sorensen

Thomas Sorensen
Macromolecular Crystallography

Thomas Sorensen Thomas Sorensen is a principal beamline scientist on the Macromolecular Beamline I02. Thomas joined Diamond at the beginning of 2005 from the Centre for Structural Biology at Aarhus University, Denmark.

Email: Thomas Sorensen
Tel: +44 (0) 1235 778464
MX Beamlines

Key Research Areas

Structural Biology, Membrane transport proteins, Beamline development

Current Research Interests

Membrane proteins are important for numerous physiological events such as signalling, transport, and bioenergetics. Approximately a third of the open reading frames in our genome are membrane proteins and an estimated half of commercially available drugs are targeted at membrane proteins.

Thomas Sorensen diagram

Structure determination is not always straightforward and membrane proteins present one of the many challenges that structural biology still faces. Membrane proteins are difficult to express, purify, and crystallise. Once crystals finally appear, they are often small and of poor quality and the modest number of known structures limit the use of molecular replacement techniques for solving the structure.

Membrane proteins may be a challenge - but it can be done. We are likely to see a great increase of the number of membrane protein structures in the PDB database over the coming years.

My main research interest is membrane transporter proteins, focusing on the primary transporters P-type ATPases and ABC transporters.

P-type ATPases
The P-type ATPases are responsible for establishing and maintaining an asymmetric distribution of a number of cations across biological membranes. To perform this task they convert chemical energy, derived from ATP, into electrochemical cation. Prominent members in eukaryotes of this primary transporter family are the Na+, K+- ATPases and H+-ATPases present in animal and plant cells, respectively. In addition P-type ATPases are involved in gastric acid secretion (H+, K+- ATPase), the transport of heavy metals, and they have also been implicated in phospholipids metabolism as "flippases".

One of the members of the family is the sarcoplasmic reticulum (SR) calcium pump (Ca2+-ATPase) from skeletal muscle (SERCA 1a). It is a 112 kDa monomeric integral membrane protein, responsible for transporting calcium ions up the electrochemical gradient from the cytoplasm into the SR. By pumping calcium away from the cytoplasm the Ca2+- ATPase terminates the muscle contraction induced by the preceding calcium release from the terminal cisternae via the dihydropyridine and ryanodine sensitive Ca2+ channels.

Studies of P-type ATPases relate to a very basic question in biology, namely to understand how cation pumps work. Our crystal structures of Ca2+- ATPase have provided us with valuable insight into how P-type ATPases are able to convert the chemical energy, derived from hydrolysis of ATP, into a vectorial mechanism for cation transport.

My ongoing research focuses on extending our understanding of the mechanism of ion pumps by looking at a number of other P-type ATPases involved in transport of other cations and heavy metals.

ABC Transporters
ABC transporters are facilitating transport of a diverse range of substrates using energy derived from ATP. They are primary transporters like the P-type ATPase, but accomplish the task in a very different way.

We are currently studying MsbA from pseudomonas aeruginosa – an ABC transporter involved in Lipid A translocation across the inner membrane. The plan is to extend our studies to mammalian ABC transporters, especially those involved in the bile salt transport as part of the enterohepatic cycle.

Beamline development and data collection
On I02 we are developing room temperature data collection by keeping samples at a known humidity during data collection. This can improve and in some cases even enable data collections from samples that struggle under cryocondition. We are also exploring what types of in-beam crystal manipulation we can do using this setup.

We are also exploring the usefulness of recording fluorescence data stream during a normal diffraction experiment to help us assess radiation damage and hence improve data processing.

Selected Publications

  1. Collagen and mature elastic fibre organisation as a function of depth in the human cornea and limbus, CS Kamma-Lorger, C Boote, S Hayes, J Moger, M Burghammer, C Knupp, AJ Quantock, T Sorensen, E Di Cola, N White, RD Young, KM Meek Journal of Structural Biology (2010) 169:424-30
  2. Crystal structure of the sodium potassium pump, J P Morth, B P Pedersen, M S Toustrup-Jensen, T L-M. Sorensen, J Petersen, J P Andersen, B Vilsen, P Nissen, Nature (2007) 450:1043-9
  3. Ca2+ versus Mg2+ coordination at the nucleotide binding site of the sarcoplasmic reticulum Ca2+-ATPase, M Picard, A-M L Jensen, T L-M Sorensen, P Champeil, J V Moller, and P Nissen, Journal of Molecular Biology (2007) 368:1-7
  4. New light for science: synchrotron radiation in structural medicine, T L-M Sorensen, KE McAuley, R Flaig, EM Duke, Trends in Biotechnology (2006) 24:500-8
  5. Membrane’s Eleven: heavy-atom derivatives of membrane-protein crystals, JP Morth, T L-M Sorensen, P Nissen, Acta Cryst. D (2006) 62:877-882
  6. Modulatory and catalytic modes of ATP binding by the calcium pump, AM Jensen, T L-M Sorensen, C Olesen, JV Moller, P Nissen, EMBO Journal (2006) 25:2305-14.
  7. Crystals of sarcoplasmic reticulum Ca2+-ATPase, T L-M Sorensen, C Olesen, AM Jensen, JV Moller, P Nissen, Journal of Biotechnology (2006) 124:704-716
  8. Dephosphorylation of the calcium pump coupled to counterion occlusion, C Olesen, T L-M Sorensen, RC Nielsen, JV Moller, P Nissen, Science (2004) 306:2251-5
  9. Phosphoryl transfer and calcium ion occlusion in the calcium pump, T L-M Sorensen, JV Moller, P Nissen, Science (2004) 304:1672-5.