Page 22 - ILLS Annual Report 2018

BIOLOGY AND HEALTH
Martine Moulin. French
Life Sciences group at the ILL
‘I work in support of the user programme of the Deuteration Laboratory. I have just received my PhD from Keele University in the UK. My thesis work, carried out in collaboration with Uppsala University (Sweden) and the Universities of
Namibia and Botswana, focused on the biophysical and structural characterisation of seed proteins from the Moringa oleifera plant, in the context of potential applications for water purification in developing areas of southern Africa.’
Deuterated cholesterol for the study of lipids and lipid cargoes in health and disease
Deutaration facility D-Lab,
fluid interfaces grazing angles
reflectomer FIGARO,
Diffractometer D16 and
Small-angle scattering diffractometer D22
Cholesterol is well known for its significance in health and disease, and in particular
for its implication in the formation of atherosclerotic plaques in heart disease
and stroke—major first-world killers. The risk factors underlying these pathologies are well known to us, through routine measurements of low-density lipoprotein (LDL—’bad cholesterol’) and high-density lipoprotein (HDL—’good cholesterol’)
in blood tests. There is considerable scientific interest in characterising the exchange kinetics between LDL and
HDL particles, which is believed to be important for an understanding of the development of plaques in blood vessels.
AUTHORS
M. Moulin (ILL) ARTICLE FROM
Chem. Phys. Lip. (2018)—doi: 10.1016/j.chemphyslip.2018.01.006
REFERENCES
[1] M. Moulin, G.A. Strohmeier, M. Hirz, K.C. Thompson, A.R. Rennie, R.A. Campbell, H. Pichler, S. Maric, V.T. Forsyth and M. Haertlein, Chem. Phys. Lip. 212 (2018) 80
[2] S. Waldie, T.K. Lind, K. Browning, M. Moulin, M. Haertlein,
V.T. Forsyth, A. Luchini, G.A. Strohmeier, H. Pichler, S. Maric and M. Cárdenas, Langmuir 34 (2018) 472
[3] A. Luchini, R. Delhom, B. Demé, V. Laux, M. Moulin, M. Haertlein, H. Pichler, G.A. Strohmeier, H. Wacklin and G. Fragneto, Colloids Surf. B. Biointerfaces 168 (2018) 126
[4] S. Waldie, M. Moulin, L. Porcar, H. Pichler, G.A. Strohmeier,
M. Skoda, V.T. Forsyth, M. Haertlein, S. Maric and M. Cárdenas, Sci. Rep. (submitted)
What is less well known is the fact that cholesterol
is a vital constituent of mammalian membranes, and whose presence in lipid bilayers has important structural consequences of direct relevance to diffusional properties and ordering within lipid bilayers. These factors, along with the nature of the lipid systems involved (and in particular the degree of lipid tail saturation), are thought to influence the location of cholesterol, which may be toward the head of the lipid molecule (in the case of saturated lipid membranes) or toward the inner interface between the two bilayer leaflets (polyunsaturated lipids). Cholesterol is also centrally involved in the structure and behaviour
of lipid rafts, which are believed to be of importance in physiological events such as signal transduction.
Neutron diffraction and neutron reflection are in many
ways ideal probes for investigating lipid interactions with molecules such as cholesterol. However, the scope of these methods is limited by the fact that the contrast (the difference in scattering length density of one component with respect to another) between protiated lipid and protiated cholesterol is very low; it is therefore extremely difficult to view either component independently of the other.
Cholesterol is a challenging molecule to produce by chemical synthesis, and the availability of perdeuterated cholesterol has been a serious limitation for neutron scattering work in this area. In collaboration with colleagues at the University of Graz (Austria) and Malmo University (Sweden), staff from the ILL’s Life Sciences Group have developed a biosynthetic method for producing perdeuterated cholesterol using the yeast Pichia pastoris (Moulin et al. [1]). Natural (‘wild type’) yeast of this type does not produce cholesterol, but instead produces a related molecule called ergosterol.
ANNUAL REPORT 2018