PhD scholarship in computational kinetic modelling of human glycolysis - DTU Biosustain

The metabolism of glucose to pyruvate, glycolysis, is seen in most organisms including humans and taught in all introductory biochemistry courses. Despite its importance, we have yet to make a precise kinetic model capturing a detailed understanding of the underlying regulatory structure. Constructing a mechanistic model of human glycolysis will pave the way for further development of targeted medicines and strain engineering of biopharmaceutical cell factories.

Thanks to recent advances in computational and analytical biology, it is now possible to reconcile mechanistic models of cell metabolism with information from quantitative multiomics experiments. In this study, we will explore human embryonic kidney (HEK) cells.

HEK cells display aerobic glycolysis, an effect first reported for cancer cells 100 years ago by Otto Warburg, where glucose is metabolised to lactate despite ample availability of oxygen to use the more efficient oxidative phosphorylation pathway. We have successfully engineered HEK cells to avoid the Warburg effect and use far less glucose, while growing at the same rate. However, the metabolic mechanisms underlying this change remain poorly understood.

This PhD student will work closely with another student who will collect multiomics data from HEK cells specifically for kinetic modelling. The focus of the current project will be to fit a kinetic model with this data and address open scientific questions about glycolysis based on the results.

These projects are funded by a Novo Nordisk Foundation Laureate grant.

Responsibilities and qualifications
You will work as part of a team to improve the kinetic modelling software developed by the group as well as integrating the multiomics measurements of HEK cells into a model of HEK glycolysis.

Kinetic modelling software is currently limited by the need to numerically approximate the solutions and gradients of large non-linear equation systems. You will work on quantitatively characterising this computational challenge and, if possible, improving on the state of the art.

As required for Danish PhD programs, you will take 30 ECTS points of relevant PhD courses.

Or a two-year master’s degree (120 ECTS points) or equivalent degree in mathematics/systems biology/bioengineering (or a similar degree with an academic level equivalent to a two-year master's degree) and have demonstrated experience in the following areas:

• Numerical methods
• Statistics
• Computational biology
• Markov Chain Monte Carlo
• Collaborative software development using modern methods and tools

Collaboration is an integral part of this project, so the candidate must demonstrate a track-record of successfully collaborating with their peers. 

Approval and Enrolment  
The scholarship for the PhD degree is subject to academic approval, and the candidate will be enrolled in one of the general degree programmes at DTU. For information about our enrolment requirements and the general planning of the PhD study programme, please see DTU's rules for the PhD education . 

We offer
DTU is a leading technical university globally recognized for the excellence of its research, education, innovation and scientific advice. We offer a rewarding and challenging job in an international environment. We strive for academic excellence in an environment characterized by collegial respect and academic freedom tempered by responsibility.

Salary and appointment terms 
The appointment will be based on the collective agreement with the Danish Confederation of Professional Associations. The allowance will be agreed upon with the relevant union. The period of employment is 3 years.

Startdate is September 1st 2024.

You can read more about career paths at DTU here .

Further information  
Further information may be obtained from Teddy Groves, https://www.biosustain.dtu.dk/ .

If you are applying from abroad, you may find useful information on working in Denmark and at DTU at DTU – Moving to Denmark . Furthermore, you have the option of joining our monthly free seminar “PhD relocation to Denmark and startup “Zoom” seminar ” for all questions regarding the practical matters of moving to Denmark and working as a PhD at DTU. 

Application procedure 
Your complete online application must be submitted no later than 13 May 2024 (23:59 Danish time) . 

Applications must be submitted as one PDF file containing all materials to be given consideration. To apply, please open the link "Apply now", fill out the online application form, and attach all your materials in English in one PDF file . The file must include:

• A letter motivating the application (cover letter)
• Curriculum vitae 
• Grade transcripts and BSc/MSc diploma (in English) including official description of grading scale

You may apply prior to ob­tai­ning your master's degree but cannot begin before having received it. 

Applications received after the deadline will not be considered.

All interested candidates irrespective of age, gender, race, disability, religion or ethnic background are encouraged to apply.

Technology for people
DTU develops technology for people. With our international elite research and study programmes, we are helping to create a better world and to solve the global challenges formulated in the UN’s 17 Sustainable Development Goals. Hans Christian Ørsted founded DTU in 1829 with a clear mission to develop and create value using science and engineering to benefit society. That mission lives on today. DTU has 13,500 students and 6,000 employees. We work in an international atmosphere and have an inclusive, evolving, and informal working environment. DTU has campuses in all parts of Denmark and in Greenland, and we collaborate with the best universities around the world.