Gertien Smits homepage
The Group
I am an assistant professor in the department of Molecular Biology and Microbial Food Safety of the Swammerdam Institute for Life Sciences of the University of Amsterdam, headed by Stanley Brul. Our group is a member of the Netherlands Institute for Systems Biology. In the group we work on the adaptive responses to changing environments, of prokaryotic and eukaryotic microorganisms.
Research interests
Stress response and adaptation in yeasts
I have always been fascinated by the fact that life on earth, based on nearly identical sets of chemical reactions for all organisms, can function in such diverse environments.
We are studying the response to environmental changes in yeasts. There are direct effects of the change on yeast physiology and cellular makeup, and there is an adaptive response which, ideally, helps the organism resume growth under the changed conditions. We ask what the effect of the change is on yeast biology, and how the adaptie response affects cellular functioning.
Student projects
Current projects
pH homeostasis and weak acid stress in Saccharomyces cerevisiae
Weak acids in yeast are thought diffuse over the plasma membrane in the undissociated form, and upon intracellular dissociationn affect intracellular pH and intracellular anion concentrations. Both aspects affect energy generating metabolism, and the adaprive response (active extrusion of potons and anions) costs energy. Additionally, lipophilic weak acids can affect memrane structure. In order to quantify the contributions of these effects to cellular growth, we aim to model the response. Therefore we first need to adequately measure intracellular (intra-organellar) pH, anion concentrations, and metabolic fluxes.
We have used the GFP-derivative pHluorin to measure cytosolic and mitochondrial pH in living cells. We are currentlymodeling the response to weak acid stress in S. cerevisiae
Contacts: drs. Rick Orij, Dr. Gertien Smits
Weak acid stress in medical and food spoilage yeasts
Various yeasts have evolved to withstand acidic environments. Zygosaccharomyces bailii is a spoilage yeast that spoils high sugar low pH beverages, and Candida albicans lives as a commensal in the oral cavity but also the acidic vagina. What mechanisms do these yeastspossess that preventthemfrom wasting energy on the constant extrusion of protons and weak acid anions? How does this compare to the adaptive response in S. cerevisiae? How relevant are these mechanisms in the virulence of C. albicans and C. glabrata?
Contacts: Azmat Ullah MSc., Dr. Gertien Smits
Heat stress and yeast metabolism
Temperature isa constantly changing environmental parameter. We studythe effect of heat stress on yeast central carbon metabolism. Increased temperature causes increased membrane fluidity, increased reaction rates, and decreased protein stability. Adaptation to these effects costs extra ATP. We ask how a yeast central carbon metabolism, crucial for generating the energy requiered for the adaptive response but affected by heat like all other pathways, is regulated in response to heat.
We adapted metabolic regulation analysis to quantify pathway flux regulation by the direct effect of temperature on enzyme kinetics, by the adaptive response through altered enzyme expression, and by thechanges in enzyme metabolic environment. Comparing different steady states, we find that, in these fully adapted conditions, hierarchical and direct temperature play oonly a minor role in the generation of a flux increase in response to a temperature increase. A high glycolytic flux at high temperature is maintained through a chenged metabolic network.
Interestingly, mitochondria and/or the TCA cycle seem to be relatively sensitive to heat, and this is the current focus of our investigations.
Contacts: Drs. Jarne Postmus and Dr. Gertien Smits
Stress tolerance acquisition
Microbes that areexposedto stress conditionsthat are non-lethal but cause growth inhibition are known to better be able to withstand high doses of the same stress. We find that many non-lethal treatments, with high and low temperature, weak acids, hydrogen peroxide, etc, cause increased resistance to acute level of heat stress, weak acid stress, and oxidative stress.
We systematicallyanalysed the biological processes important for acute stress tolerance, using the yeast haploid barcoded deletion collection.We find that, although specific processes are requiredfor survivalofspecific stresses, growth rate is a general determinant of stress survival. This is true for the mutants, but also forwild-type. Also, growth rate reduction by a non-lethal treatment is a main determinat for stress tolerance acquisition. We hypothesize that growth rate and stress tolerance processes are communicating vessels, and that growth rate reduction is an important aspect of adaptation to environmental change.
Contact: Dr. Gertien Smits
Teaching
I teach about the intricate molecular collaborations that make a cell tick in the following courses
BSc Biology
Cellular Signaling (B231 6EC)
Cellular Physiology (B232 6EC)
Molecular Cell Biology (B206 12EC)
BSc Biomedical Sciences
Cell Biology (BW202 6EC)
Molecular Cell Biology (BW206 12EC)
BSc Bio-exact
Systems Biology 2 (6EC)
BSc Chemistry
Cellular Biochemistry (3EC)
In both bachelor and master phase I supervise research internships and literaturetheses (see student projects)
Furthermore I am chairman of the Board of Education for Biology, Biological Sciences and Life Sciences
Other activities
IMC weekendschool
Course in Microbiology for children in the final grade of primary school in Amsterdam Zuidoost, 3 sundays of microbiology knowledge, formulating and testing of hypotheses based on knowledge, and experimentation
NEMO wakker worden lezingen
Sunday morning lecture in the Amsterdam Science museum NEMO for children from 8-12 years old
IMC weekendschool
NEMO wakker worden lezing (dutch)