Ústav fyzikální chemie J. Heyrovského AV ČR, v. v. i. vyhlašuje v souladu se zákonem č. 283/1992 Sb. o Akademii věd České republiky, ve znění zákona č. 420/2005 Sb. a Stanov AV ČR výběrové řízení na pozici Fully funded PhD positions in computational biophysics and biomolecular modeling.
The research team led by Dr. Štěpán Timr at J. Heyrovský Institute of Physical Chemistry in Prague offers fully funded PhD positions in computational biophysics and biomolecular modeling.
Are you fascinated by the complexity of the interior of living cells? Do you enjoy constructing models of proteins and other biomolecules in the computer? Would you like to use the tools of physics, chemistry, and mathematics to describe processes in cells?
We are a research group focusing on the computer simulation of the cell interior. Using multi-scale molecular models, we aim to elucidate physical and chemical mechanisms governing the organization of metabolic pathways in living cells. Our research team, supported by the prestigious Lumina Quaeruntur Award as well as by a grant from the Czech Science Foundation, is integrated into the young and interdisciplinary Department of Computational Chemistry, connecting the physical chemistry and biophysics of proteins and membranes with theoretical enzymology and spectroscopy.
PhD project 1: Effect of intracellular environment on enzyme function
Metabolic reactions take place in a highly crowded cellular interior, which is filled with proteins, nucleic acids, metabolites, and other biological molecules. How interactions with such a dense and heterogeneous environment influence—and potentially control—enzyme activity, has not been fully elucidated yet. Understanding these effects would benefit from detailed atomistic insights provided by molecular simulations. The goal of this PhD work will be to link the composition and structure of the local environment around an enzyme to key factors determining enzyme activity, such as the conformational state of the enzyme molecule and binding preferences of its substrates. To reach this goal, the PhD student will establish a computational protocol combining enhanced-sampling molecular simulations with machine-learning approaches. He/she will apply the protocol to systems of growing complexity, ranging from experimentally thoroughly-characterized model systems to complex models of biomolecular condensates involving intrinsically disordered proteins and/or RNA. The results of the work will form an important building block of a multi-scale description of dynamic enzyme assemblies and their role in the regulation of cellular metabolism.
PhD project 2: Computational modeling of dynamic enzyme assemblies
In living cells, various enzymes have been found to assemble into transient structures that can appear and disassemble as a function of external conditions. Among other examples, such dynamic assemblies have been identified in glycolysis or in the purine synthesis pathway. Recent experimental evidence points to a key role of dynamic enzyme assemblies in the regulation and adaptation of cellular metabolism, including their possible role as a switch between two or more competing pathways. However, the mechanisms underlying the formation and function of these assemblies are yet to be elucidated. By using a combination of atomistic, coarse-grained and ultra-coarse-grained molecular modeling and working in tight connection with experimental data, the PhD student will characterize molecular interactions promoting assembly formation and quantify the diffusivities of enzymes and reactants inside dynamic enzyme assemblies. In particular, he/she will evaluate the potential for substrate channeling, that is, passing the intermediate products efficiently between consecutive enzymes of a pathway. The computational methodology developed in this work will serve as a basis for the prediction of metabolic fluxes given a composition and architecture of an enzyme assembly.
PhD project 3: Mechanisms of allostery and regulation in glycolysis
Glycolysis is a key metabolic pathway, forming a starting point of several other important pathways. As such, it is subjected to extensive regulation allowing it to respond to the cell’s varying demands of energy and building blocks. However, molecular details of this complex regulation are still not fully understood. In this work, the PhD student will use a variety of computational approaches, including molecular dynamics simulations coupled with enhanced-sampling techniques, to elucidate the mechanisms of allosteric regulation of glycolysis by cellular energy signals. A focus of the work will be on PFK1, a rate-limiting enzyme forming a “gatekeeper” of glycolysis. The work will benefit from the currently expanding set of available structural data of glycolytic enzymes, including data obtained by our experimental collaborators.
The candidates are expected to hold a MSc (or an equivalent) in physics, chemistry, or related fields before the start of the position. They should be interested in biomolecules and motivated to learn new things. Moreover, they should possess good computer skills and be fluent in English. Experience with molecular simulations and programming would be a plus. The successful candidates will enroll at Charles University in Prague, the top-ranking university in the Czech Republic.
Application deadline: March 20, 2023
Starting date: Summer 2023 (no later than October 1)
Type of contract: Temporary
Job status: Full time
25 days paid leave of absence (holidays) per year + 3 days of paid sick-leave in addition to the statutory insurance
Flexible working-time, the possibility of part-time work, work-life balance
Subsidy for sports and cultural activities
Recreation subsidy, recreation subsidy for children
Possibility of attending children groups of the CAS
Possibility to use discounts in recreation centers of the CAS
Sports goods rental, free parking, trade union library
Health and social insurance paid mandatory by the institute
If you are interested, please send us your CV together with your motivation letter, transcripts of all courses and grades, and two contacts as a reference to [email protected] Please indicate in your application which of the three PhD projects listed above you would be primarily interested in. Please write in the subject line of your email SC2023_04. For any technical questions, contact [email protected]
By providing us your personal data in your CV, you have allowed J. Heyrovský Institute of Physical Chemistry to process and file your CV in the HR database. Your personal data will be used for the internal HR needs of the J. Heyrovský Institute of Physical Chemistry only. At the same time you confirm herewith that the personal data as stated in the CV you have sent to us is true and accurate.
Uzávěrka přihlášek: 20. 03. 2023
Dovolujeme si Vás informovat, že zasláním odpovědi na inzerát poskytujete příslušnému správci své osobní údaje, a to za účelem realizace výběrového řízení a uzavření pracovní smlouvy nebo dohody (DPP, DPČ) ohledně Vámi vybrané pozice. Toto zpracování Vašich osobních údajů bude prováděno na právním základě splnění smlouvy dle 6 odst. 1 písm. b) obecného nařízení o ochraně osobních údajů (GDPR). Vaše osobní údaje budou zpracovávány pouze v nezbytném rozsahu a pouze po dobu trvání výběrového řízení na danou pozici. Zpracování Vašich osobních údajů bude dostatečně zabezpečeno, Vaše osobní údaje nebudou bez Vašeho souhlasu předávány třetím osobám. V souladu s příslušnými právními předpisy Vás informujeme, že máte právo (i) na přístup k osobním údajům, (ii) na opravu či doplnění nepřesných nebo nepravdivých osobních údajů, (iii) na výmaz osobních údajů, (iv) na omezení zpracování osobních údajů ve zvláštních případech, (v) na přenositelnost údajů, (vi) vznést námitku proti zpracování a (vii) obrátit se na Úřad pro ochranu osobních údajů.