Anni Kumari

Name: Anni Kumari

Nationality: Indian

Academic Background: M.Sc. Biotechnology

Project Title: On the molecular mechanism for regulating lipoprotein lipase activity

Project Background:  All living beings (and so do we), require energy to perform the vital functions starting from small cellular processes to complex bodily functions. This energy requirement is fulfilled by our dietary intake. Our cells provide energy to us by metabolizing components of our food.

Our dietary components can be broadly classified into three categories, namely carbohydrates, proteins and lipids (or fats).The amount of energy produced by the breakdown of these biomolecules differs. I am currently working with the third component. One of the defining characteristics of fats is that they are insoluble in water. Another nice little fact about them is that, these fats, depending on their structure (for instance, how big are their alkyl chains), produce energy after breakdown, which is at times double than that of the same weight of sugars and proteins. Research over the years has led to promising insights in understanding how these lipid molecules are stored, catabolized and how deviations from the usual processing of these lipids and fats (due to certain mutations, diseases of a different origin or others factors hindering the usual process) lead to disease development and progression.

So at last in short, we all want to have a better understanding of what makes a good dietary intake. We also want to have a good understanding of the factors involved in our basic metabolism. And, that’s what makes my current research interesting as it would lead to bridging some of the underlying gaps and further deeper insights into the mechanism of lipoprotein lipase (my enzyme of interest) mediated triglyceride metabolism.

Project Aim: Lipids are one of the principal energy-yielding biomolecules. The long alkyl chains present in triglycerides can yield a very significant amount of energy. Apolipoprotein C-II (Apo C-II) plays an essential role in plasma triglyceride metabolism. Mutations in Apo C-II lead to hyperlipoproteinemia type IB, characterized by hypertriglyceridemia, xanthomas, increased risk of pancreatitis and early atherosclerosis. It has already been well established that Apo C-II, through its C-terminal helix, acts as an activator for the enzyme Lipoprotein lipase (LPL) which in turn hydrolyzes triglycerides.

The project aims to focus on understanding the molecular mode of action of Apo C-II in terms of its role as an activator of LPL. With the advantageous availability of the LPL structure, we now look forward to mapping the key amino acids in the active-site region of Apo-CII – LPL interaction through MicroScale Thermophoresis (MST) and Surface Plasmon Resonance (SPR). We also plan to investigate the resulting enzyme activity and critical conformational changes in the secondary structure of Apo-CII and LPL domains using Hydrogen-deuterium exchange mass spectrometry (HDX-MS). 

Expected Outcome:  Understanding of the degree of impact that ApoC-II has on lipoprotein lipase activity. We will also have a good understanding of ApoC-II itself from it’s biophysical characterization. Mapping the regions where the lipoprotein lipase interacts with ApoC-II, which would be beneficial for better understanding of the mechanism of triglyceride metabolism and hence, aid in the development of new therapeutic approaches in future.

Contact:  anni.kumari@finsenlab.dk and anni.kumari@bric.ku.dk