The role of mitochondrial function in health and disease has become increasingly recognized, particularly in the last two decades. Mitochondrial dysfunction as well as disruptions of cellular bioenergetics have been shown to be ubiquitous in some of the most prevalent diseases in our society, such as type 2 diabetes, cardiovascular disease, metabolic syndrome, cancer, and Alzheimer’s disease. However, the etiology and pathogenesis of mitochondrial dysfunction in multiple diseases have yet to be elucidated, making it one of the most significant medical challenges in our history. [*]

FAHD proteins are members of the FAH superfamily of metabolic enzymes, the physiological role of which is only partially explored [*]. In the case of FAHD1, existing evidence suggests that it is a mitochondrial protein which can catalyze hydrolysis of acylpyruvates and the decarboxylation of oxaloacetate. However, several features of FAHD1 activity remain largely unexplored, in particular due to the fact that experiments with FAHD1/2 depleted cells and animals still lack considerable mechanistic detail. The main purpose of this review is to stimulate discussions in this understudied field of research, and to critically review the research agenda how to unmask molecular mechanisms of action for these proteins.
We propose a model of how FAHD1 catalytic activity as oxaloacetate decarboxylase in mitochondria may describe FAHD1 as a regulator of TCA cycle flux and as a possible regulator of mitochondrial function and senescence [*]. It is well reported that FAHD1 expression in human organs correlates with the regulation of calcium metabolism in the human body, and experimental results described in this work are in line with the hypothesis that FAHD1 may be a calcium binding protein. Calcium binding proteins are present in various cellular compartments and serve to mediate effects of increased calcium concentration on biological responses [*].

Cellular senescence is a phenomenon characterized by the cessation of cell division. Senescent cells are unique in that they eventually stop multiplying but don't die off when they should. We investigate mechanisms that effect the onset and development of cellular senecence, in order to better undertstand the principles behind the complex aging process of higher organisms.

Substantial efforts are currently being made towards the discovery of novel and more specific biomarkers, optimized combinatorial strategies and the development of emerging detection techniques for cellular senescence. The reliable assessment and identification of senescence is not only crucial for better understanding its underlying biology, but also imperative for the development of diagnostic and therapeutic strategies aimed at targeting senescence in the clinic [*]. In our lab, we employ common methods to study the onset of cellular senescence in in vitro cell models.

Caenorhabditis elegans is one of the outstanding model organisms used for aging research because of its very short lifespan and simple physiology. Moreover, experiments with C. elegans are free of ethical concerns. Many breakthrough discoveries in the field of aging research have been made using C. elegans, inluding the finding that certain lifespan increasing mutations in C. elegans were found to delay aging by impinging several signaling pathways and related epigenetic modifications, including the insulin/IGF-1 signaling (IIS), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR) pathways [*]. In our lab, we employ common methods to study the onset of cellular senescence in this model system.

Computer-aided biology (CAB) is the term given to a suite of tools that augment human capabilities in biological research. It can include software for simulating and designing biological systems, as well as systems that can design, simulate, optimise and execute experiments. [*]

We perform in silico Molecular Dynamics simulations, Monte Carlo optimization and docking experiments, to supplement our research data with models and physico-chemical data. Related to our focus on cancer research, we work on the indentification and synthesis of novel FAHD1 inhibitros, to be possibly used as anti-cancer drugs [*]. We develop and maintain the software packages QuMuLuS++ and QMCF2.

The use and development of computer systems that are able to learn and adapt without following explicit instructions, by using algorithms and statistical models to analyse and draw inferences from patterns in data, has already become a basic requirement for modern research. We employ and partly develop such algorithms, to be used in special applications retaled to our major research focus.